Andrew D. Bowser

NEW YORK – The cell therapy landscape increasingly involves strategies beyond chimeric antigen receptor (CAR) T-cell therapy, but those studies still predominate among investigational trials, according to Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa.

Researchers are looking at CAR T-cell therapy for earlier lines of treatment, especially in patients with aggressive lymphomas, Dr. Locke said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Of 753 trials examining cell therapies and listed at ClinicalTrials.gov as of March 30, 2018, about half (404) were CAR T-cell therapies. The others included T-cell receptor therapies, tumor infiltrating lymphocyte therapies, dendritic cell vaccines, and natural killer cell–based therapies, according to an article in Nature Reviews.

“The development isn’t just here in the United States,” Dr. Locke said. “It’s really global. We see a lot of activity in Europe, but also in China. We’re seeing medical advances across the world through molecular biology and gene engineering of T cells and other immune cells which can be adoptively transferred into patients.”

That activity includes studies seeking to move CAR T-cell therapy earlier in the treatment paradigm for some diseases, he added. “CAR T-cell therapy in non-Hodgkin lymphoma is really beginning a paradigm shift, at least in my mind.”

Several large, randomized trials that are now comparing CD19 CAR T-cell therapy with second-line standard-of-care therapies for patients with aggressive B-cell lymphomas. Among those trials is ZUMA-7, a phase 3, randomized trial comparing axicabtagene ciloleucel with standard-of-care treatment in patients with relapsed or refractory diffuse large B-cell lymphoma.

While prognosis remains poor for relapsed or progressing aggressive B-cell lymphomas treated with chemotherapy, data to date suggest CAR T-cell therapy produces durable, long-term remissions in about 40% of patients at “a year out and counting,” Dr. Locke said.

He presented a proposed treatment algorithm that included R-CHOP chemotherapy up front and CAR T-cell therapy in later lines of treatment, an approach that Dr. Locke speculated could result in a cure rate of perhaps 80% in large-cell lymphomas.

Encouraging longer-term data is emerging, with some patients with aggressive T-cell lymphomas now without recurrence for 5 years or more following a single infusion of CAR T-cell therapy, he said.

Dr. Locke reported a financial disclosure related to Cellular Biomedicine Group.

NEW YORK – The cell therapy landscape increasingly involves strategies beyond chimeric antigen receptor (CAR) T-cell therapy, but those studies still predominate among investigational trials, according to Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa.

Researchers are looking at CAR T-cell therapy for earlier lines of treatment, especially in patients with aggressive lymphomas, Dr. Locke said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Of 753 trials examining cell therapies and listed at ClinicalTrials.gov as of March 30, 2018, about half (404) were CAR T-cell therapies. The others included T-cell receptor therapies, tumor infiltrating lymphocyte therapies, dendritic cell vaccines, and natural killer cell–based therapies, according to an article in Nature Reviews.

“The development isn’t just here in the United States,” Dr. Locke said. “It’s really global. We see a lot of activity in Europe, but also in China. We’re seeing medical advances across the world through molecular biology and gene engineering of T cells and other immune cells which can be adoptively transferred into patients.”

That activity includes studies seeking to move CAR T-cell therapy earlier in the treatment paradigm for some diseases, he added. “CAR T-cell therapy in non-Hodgkin lymphoma is really beginning a paradigm shift, at least in my mind.”

Several large, randomized trials that are now comparing CD19 CAR T-cell therapy with second-line standard-of-care therapies for patients with aggressive B-cell lymphomas. Among those trials is ZUMA-7, a phase 3, randomized trial comparing axicabtagene ciloleucel with standard-of-care treatment in patients with relapsed or refractory diffuse large B-cell lymphoma.

While prognosis remains poor for relapsed or progressing aggressive B-cell lymphomas treated with chemotherapy, data to date suggest CAR T-cell therapy produces durable, long-term remissions in about 40% of patients at “a year out and counting,” Dr. Locke said.

He presented a proposed treatment algorithm that included R-CHOP chemotherapy up front and CAR T-cell therapy in later lines of treatment, an approach that Dr. Locke speculated could result in a cure rate of perhaps 80% in large-cell lymphomas.

Encouraging longer-term data is emerging, with some patients with aggressive T-cell lymphomas now without recurrence for 5 years or more following a single infusion of CAR T-cell therapy, he said.

Dr. Locke reported a financial disclosure related to Cellular Biomedicine Group.

NEW YORK – The cell therapy landscape increasingly involves strategies beyond chimeric antigen receptor (CAR) T-cell therapy, but those studies still predominate among investigational trials, according to Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa.

Researchers are looking at CAR T-cell therapy for earlier lines of treatment, especially in patients with aggressive lymphomas, Dr. Locke said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Of 753 trials examining cell therapies and listed at ClinicalTrials.gov as of March 30, 2018, about half (404) were CAR T-cell therapies. The others included T-cell receptor therapies, tumor infiltrating lymphocyte therapies, dendritic cell vaccines, and natural killer cell–based therapies, according to an article in Nature Reviews.

“The development isn’t just here in the United States,” Dr. Locke said. “It’s really global. We see a lot of activity in Europe, but also in China. We’re seeing medical advances across the world through molecular biology and gene engineering of T cells and other immune cells which can be adoptively transferred into patients.”

That activity includes studies seeking to move CAR T-cell therapy earlier in the treatment paradigm for some diseases, he added. “CAR T-cell therapy in non-Hodgkin lymphoma is really beginning a paradigm shift, at least in my mind.”

Several large, randomized trials that are now comparing CD19 CAR T-cell therapy with second-line standard-of-care therapies for patients with aggressive B-cell lymphomas. Among those trials is ZUMA-7, a phase 3, randomized trial comparing axicabtagene ciloleucel with standard-of-care treatment in patients with relapsed or refractory diffuse large B-cell lymphoma.

While prognosis remains poor for relapsed or progressing aggressive B-cell lymphomas treated with chemotherapy, data to date suggest CAR T-cell therapy produces durable, long-term remissions in about 40% of patients at “a year out and counting,” Dr. Locke said.

He presented a proposed treatment algorithm that included R-CHOP chemotherapy up front and CAR T-cell therapy in later lines of treatment, an approach that Dr. Locke speculated could result in a cure rate of perhaps 80% in large-cell lymphomas.

Encouraging longer-term data is emerging, with some patients with aggressive T-cell lymphomas now without recurrence for 5 years or more following a single infusion of CAR T-cell therapy, he said.

Dr. Locke reported a financial disclosure related to Cellular Biomedicine Group.

NEW YORK – Although optimal sequencing strategies in chronic lymphocytic leukemia are still unclear, real-world data suggest an alternate kinase inhibitor or venetoclax is the best approach for a patient who has received ibrutinib or idelalisib, according to John N. Allan, MD, of Cornell University, New York.

©Ed Uthman/Flickr

“I think for the most part, there’s enough evidence,” Dr. Allan said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“If you had one to two lines of therapy, it still favors the novel agents rather than the chemotherapy arms in all these studies,” said Dr. Allan, referring to some of the pivotal trials supporting approval of novel agents in chronic lymphocytic leukemia (CLL). “The earlier we get to these drugs, I believe, the better.”

While venetoclax after ibrutinib is supported by multiple studies, “vice versa is unknown, but there’s seemingly no reason to think it wouldn’t work – different mechanisms of actions, different pathways,” Dr. Allan said.

What is clear, he added, is that retreating those patients with chemoimmunotherapy is not optimal.

In support of that, he cited a multicenter retrospective analysis, which is believed to be the largest real-world experience to date of novel agents in CLL looking at post–kinase inhibitor salvage strategies (Ann Oncol. 2017 May 1;28[5]:1050-6).

Using an alternate kinase inhibitor or venetoclax resulted in superior progression-free survival versus chemoimmunotherapy at the time of initial kinase inhibitor failure in that study, which looked at treatment strategies and outcomes for 683 patients.

Ibrutinib appeared to be superior to idelalisib as a first kinase inhibitor, with significantly better progression-free survival in both frontline and relapsed/refractory settings, and in both complex karyotype and del17p patients, according to the report. Additionally, the response rate to venetoclax seemed superior to that of idelalisib in patients who discontinued ibrutinib because of progression or toxicity.

All of that supports the need for trials to test various sequencing strategies and establish clear treatment algorithms, according to Dr. Allan. “Optimal sequencing is unknown, but real-world data gives us some idea.”

For relapsed/refractory patients, ibrutinib, idelalisib, and venetoclax all have lengthened responses, improved survival, and are approved by the Food and Drug Administration, he added, noting that the toxicity profiles vary and must be understood when dosing and prescribing these agents.

More novel treatments are on the way. On Sept. 24, just days after Dr. Allan’s NCCN presentation, the FDA granted approval to duvelisib for adults with relapsed or refractory CLL or small lymphocytic lymphoma following two or more previous lines of therapy.

Dr. Allan reported financial disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis Pharmaceuticals, and Verastem Oncology.

NEW YORK – Although optimal sequencing strategies in chronic lymphocytic leukemia are still unclear, real-world data suggest an alternate kinase inhibitor or venetoclax is the best approach for a patient who has received ibrutinib or idelalisib, according to John N. Allan, MD, of Cornell University, New York.

©Ed Uthman/Flickr

“I think for the most part, there’s enough evidence,” Dr. Allan said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“If you had one to two lines of therapy, it still favors the novel agents rather than the chemotherapy arms in all these studies,” said Dr. Allan, referring to some of the pivotal trials supporting approval of novel agents in chronic lymphocytic leukemia (CLL). “The earlier we get to these drugs, I believe, the better.”

While venetoclax after ibrutinib is supported by multiple studies, “vice versa is unknown, but there’s seemingly no reason to think it wouldn’t work – different mechanisms of actions, different pathways,” Dr. Allan said.

What is clear, he added, is that retreating those patients with chemoimmunotherapy is not optimal.

In support of that, he cited a multicenter retrospective analysis, which is believed to be the largest real-world experience to date of novel agents in CLL looking at post–kinase inhibitor salvage strategies (Ann Oncol. 2017 May 1;28[5]:1050-6).

Using an alternate kinase inhibitor or venetoclax resulted in superior progression-free survival versus chemoimmunotherapy at the time of initial kinase inhibitor failure in that study, which looked at treatment strategies and outcomes for 683 patients.

Ibrutinib appeared to be superior to idelalisib as a first kinase inhibitor, with significantly better progression-free survival in both frontline and relapsed/refractory settings, and in both complex karyotype and del17p patients, according to the report. Additionally, the response rate to venetoclax seemed superior to that of idelalisib in patients who discontinued ibrutinib because of progression or toxicity.

All of that supports the need for trials to test various sequencing strategies and establish clear treatment algorithms, according to Dr. Allan. “Optimal sequencing is unknown, but real-world data gives us some idea.”

For relapsed/refractory patients, ibrutinib, idelalisib, and venetoclax all have lengthened responses, improved survival, and are approved by the Food and Drug Administration, he added, noting that the toxicity profiles vary and must be understood when dosing and prescribing these agents.

More novel treatments are on the way. On Sept. 24, just days after Dr. Allan’s NCCN presentation, the FDA granted approval to duvelisib for adults with relapsed or refractory CLL or small lymphocytic lymphoma following two or more previous lines of therapy.

Dr. Allan reported financial disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis Pharmaceuticals, and Verastem Oncology.

NEW YORK – Although optimal sequencing strategies in chronic lymphocytic leukemia are still unclear, real-world data suggest an alternate kinase inhibitor or venetoclax is the best approach for a patient who has received ibrutinib or idelalisib, according to John N. Allan, MD, of Cornell University, New York.

©Ed Uthman/Flickr

“I think for the most part, there’s enough evidence,” Dr. Allan said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“If you had one to two lines of therapy, it still favors the novel agents rather than the chemotherapy arms in all these studies,” said Dr. Allan, referring to some of the pivotal trials supporting approval of novel agents in chronic lymphocytic leukemia (CLL). “The earlier we get to these drugs, I believe, the better.”

While venetoclax after ibrutinib is supported by multiple studies, “vice versa is unknown, but there’s seemingly no reason to think it wouldn’t work – different mechanisms of actions, different pathways,” Dr. Allan said.

What is clear, he added, is that retreating those patients with chemoimmunotherapy is not optimal.

In support of that, he cited a multicenter retrospective analysis, which is believed to be the largest real-world experience to date of novel agents in CLL looking at post–kinase inhibitor salvage strategies (Ann Oncol. 2017 May 1;28[5]:1050-6).

Using an alternate kinase inhibitor or venetoclax resulted in superior progression-free survival versus chemoimmunotherapy at the time of initial kinase inhibitor failure in that study, which looked at treatment strategies and outcomes for 683 patients.

Ibrutinib appeared to be superior to idelalisib as a first kinase inhibitor, with significantly better progression-free survival in both frontline and relapsed/refractory settings, and in both complex karyotype and del17p patients, according to the report. Additionally, the response rate to venetoclax seemed superior to that of idelalisib in patients who discontinued ibrutinib because of progression or toxicity.

All of that supports the need for trials to test various sequencing strategies and establish clear treatment algorithms, according to Dr. Allan. “Optimal sequencing is unknown, but real-world data gives us some idea.”

For relapsed/refractory patients, ibrutinib, idelalisib, and venetoclax all have lengthened responses, improved survival, and are approved by the Food and Drug Administration, he added, noting that the toxicity profiles vary and must be understood when dosing and prescribing these agents.

More novel treatments are on the way. On Sept. 24, just days after Dr. Allan’s NCCN presentation, the FDA granted approval to duvelisib for adults with relapsed or refractory CLL or small lymphocytic lymphoma following two or more previous lines of therapy.

Dr. Allan reported financial disclosures related to AbbVie, Acerta Pharma, Genentech, Pharmacyclics, Sunesis Pharmaceuticals, and Verastem Oncology.

NEW YORK – Although the data set is small and not yet mature, chimeric antigen receptor (CAR) T-cell therapy appears to be a promising approach for Hodgkin lymphoma, according to Philippe Armand, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center and the Massachusetts General Hospital Cancer Center in Boston.

While based on a handful of patients, the data do suggest this approach may play a role by targeting CD30 or Epstein Barr virus (EBV), Dr. Armand said at the NCCN Annual Congress: Hematologic Malignancies.

“Most importantly perhaps, like its experience outside of Hodgkin lymphoma, it may really have curative potential, based on the long [complete response] rates that have been already exhibited,” he said.

Much of the published clinical experience to date is with CD30-directed CAR Ts, Dr. Armand said, noting that in Hodgkin lymphoma, results so far show promise for this particular approach.

In a recent phase 1 dose escalation study, nine patients with relapsed/refractory Hodgkin lymphoma or anaplastic large-cell lymphoma (ALCL) received infusions of autologous T cells modified to express CD30-specific CAR T cells encoding the CD28 costimulatory domain, with no conditioning regimen.

Out of seven relapsed Hodgkin lymphoma patients, one had a complete response (CR) lasting beyond 2.5 years following a second infusion. Another patient had a CR persisting almost 2 years, and three patients had transient stable disease. One of the two ALCL patients had a CR lasting 9 months after a fourth infusion.

No toxicities attributable to the therapy were seen, according to the investigators.

The CD30 CAR T cells are being evaluated with a conditioning regimen in the phase 1 RELY-30 trial. Preliminary results presented at the 2018 European Society for Blood and Marrow Transplantation meeting in Lisbon showed better expansion of CAR T cells and responses in three out of five patients, including two CRs, according to Dr. Armand.

A CD30-directed CAR T-cell therapy with a 4-1BB costimulatory domain has also been tested in a small group of Hodgkin patients with a response rate of 35% – including some CRs – with an apparent lower response rate in patients with extranodal involvement. Dr. Armand noted that those findings need to be validated in additional studies.

Among non CD-30 targeted products, a CD19 CAR-T approach has been tried in Hodgkin lymphoma, though preliminary results suggest only transient activity, according to the presenter.

One interesting approach has been the targeting of EBV, he added. Recently reported results showed that two doses of T cells with specificity for EBV-derived tumor antigens induced clinical responses in patients with EBV-positive Hodgkin lymphoma.

The cells were engineered to express dominant-negative TGF-beta receptor type 2, according to the report. “We know that TGF-beta provides a strong immunosuppressant signal in the tumor microenvironment,” Dr. Armand said, noting that some of the responses in the seven evaluable patients lasted 4 years or more.

Dr. Armand reported financial disclosures related to Adaptive Biotechnologies/Sequenta, Affimed, Bristol-Myers Squibb, Merck, and Roche.
 

NEW YORK – Although the data set is small and not yet mature, chimeric antigen receptor (CAR) T-cell therapy appears to be a promising approach for Hodgkin lymphoma, according to Philippe Armand, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center and the Massachusetts General Hospital Cancer Center in Boston.

While based on a handful of patients, the data do suggest this approach may play a role by targeting CD30 or Epstein Barr virus (EBV), Dr. Armand said at the NCCN Annual Congress: Hematologic Malignancies.

“Most importantly perhaps, like its experience outside of Hodgkin lymphoma, it may really have curative potential, based on the long [complete response] rates that have been already exhibited,” he said.

Much of the published clinical experience to date is with CD30-directed CAR Ts, Dr. Armand said, noting that in Hodgkin lymphoma, results so far show promise for this particular approach.

In a recent phase 1 dose escalation study, nine patients with relapsed/refractory Hodgkin lymphoma or anaplastic large-cell lymphoma (ALCL) received infusions of autologous T cells modified to express CD30-specific CAR T cells encoding the CD28 costimulatory domain, with no conditioning regimen.

Out of seven relapsed Hodgkin lymphoma patients, one had a complete response (CR) lasting beyond 2.5 years following a second infusion. Another patient had a CR persisting almost 2 years, and three patients had transient stable disease. One of the two ALCL patients had a CR lasting 9 months after a fourth infusion.

No toxicities attributable to the therapy were seen, according to the investigators.

The CD30 CAR T cells are being evaluated with a conditioning regimen in the phase 1 RELY-30 trial. Preliminary results presented at the 2018 European Society for Blood and Marrow Transplantation meeting in Lisbon showed better expansion of CAR T cells and responses in three out of five patients, including two CRs, according to Dr. Armand.

A CD30-directed CAR T-cell therapy with a 4-1BB costimulatory domain has also been tested in a small group of Hodgkin patients with a response rate of 35% – including some CRs – with an apparent lower response rate in patients with extranodal involvement. Dr. Armand noted that those findings need to be validated in additional studies.

Among non CD-30 targeted products, a CD19 CAR-T approach has been tried in Hodgkin lymphoma, though preliminary results suggest only transient activity, according to the presenter.

One interesting approach has been the targeting of EBV, he added. Recently reported results showed that two doses of T cells with specificity for EBV-derived tumor antigens induced clinical responses in patients with EBV-positive Hodgkin lymphoma.

The cells were engineered to express dominant-negative TGF-beta receptor type 2, according to the report. “We know that TGF-beta provides a strong immunosuppressant signal in the tumor microenvironment,” Dr. Armand said, noting that some of the responses in the seven evaluable patients lasted 4 years or more.

Dr. Armand reported financial disclosures related to Adaptive Biotechnologies/Sequenta, Affimed, Bristol-Myers Squibb, Merck, and Roche.
 

NEW YORK – Although the data set is small and not yet mature, chimeric antigen receptor (CAR) T-cell therapy appears to be a promising approach for Hodgkin lymphoma, according to Philippe Armand, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center and the Massachusetts General Hospital Cancer Center in Boston.

While based on a handful of patients, the data do suggest this approach may play a role by targeting CD30 or Epstein Barr virus (EBV), Dr. Armand said at the NCCN Annual Congress: Hematologic Malignancies.

“Most importantly perhaps, like its experience outside of Hodgkin lymphoma, it may really have curative potential, based on the long [complete response] rates that have been already exhibited,” he said.

Much of the published clinical experience to date is with CD30-directed CAR Ts, Dr. Armand said, noting that in Hodgkin lymphoma, results so far show promise for this particular approach.

In a recent phase 1 dose escalation study, nine patients with relapsed/refractory Hodgkin lymphoma or anaplastic large-cell lymphoma (ALCL) received infusions of autologous T cells modified to express CD30-specific CAR T cells encoding the CD28 costimulatory domain, with no conditioning regimen.

Out of seven relapsed Hodgkin lymphoma patients, one had a complete response (CR) lasting beyond 2.5 years following a second infusion. Another patient had a CR persisting almost 2 years, and three patients had transient stable disease. One of the two ALCL patients had a CR lasting 9 months after a fourth infusion.

No toxicities attributable to the therapy were seen, according to the investigators.

The CD30 CAR T cells are being evaluated with a conditioning regimen in the phase 1 RELY-30 trial. Preliminary results presented at the 2018 European Society for Blood and Marrow Transplantation meeting in Lisbon showed better expansion of CAR T cells and responses in three out of five patients, including two CRs, according to Dr. Armand.

A CD30-directed CAR T-cell therapy with a 4-1BB costimulatory domain has also been tested in a small group of Hodgkin patients with a response rate of 35% – including some CRs – with an apparent lower response rate in patients with extranodal involvement. Dr. Armand noted that those findings need to be validated in additional studies.

Among non CD-30 targeted products, a CD19 CAR-T approach has been tried in Hodgkin lymphoma, though preliminary results suggest only transient activity, according to the presenter.

One interesting approach has been the targeting of EBV, he added. Recently reported results showed that two doses of T cells with specificity for EBV-derived tumor antigens induced clinical responses in patients with EBV-positive Hodgkin lymphoma.

The cells were engineered to express dominant-negative TGF-beta receptor type 2, according to the report. “We know that TGF-beta provides a strong immunosuppressant signal in the tumor microenvironment,” Dr. Armand said, noting that some of the responses in the seven evaluable patients lasted 4 years or more.

Dr. Armand reported financial disclosures related to Adaptive Biotechnologies/Sequenta, Affimed, Bristol-Myers Squibb, Merck, and Roche.
 

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

Digitally delivered cognitive-behavioral therapy not only improved insomnia, but also provided “around-the-clock” health, psychological, and quality-of-life improvements, according to investigators.

Hocus Focus Studio/iStockphoto

Compared with control subjects, patients who used a cognitive-behavioral therapy (CBT) program and associated iPhone app had small improvements in functional health and psychological well-being and large improvements in sleep-related quality of life, the investigators reported.

Those changes were mediated by a large improvement in insomnia, according to Colin A. Espie, PhD, professor of sleep medicine at the University of Oxford (England), and his colleagues.

“These findings indicate that digital CBT improves both daytime and nighttime aspects of insomnia, lending further weight to the clinical guideline recommendation of CBT as the treatment of choice for insomnia,” Dr. Espie and his colleagues reported in JAMA Psychiatry.

Their study included 1,711 adults with symptoms of insomnia that were self-reported and a score of 16 or less on the Sleep Condition Indicator (SCI), which has a range of 0-32. A total of 853 were randomized to receive digital CBT, of whom 413 completed six scheduled 20-minute sessions; an additional 276 adults completed at least one session. The control arm included 858 individuals randomized to sleep hygiene education, of whom 759 went on to receive that intervention.

Small but significant improvements were seen in self-reported measures of functional health, Dr. Espie and his colleagues reported. The adjusted differences in mean scores on the Patient-Reported Outcomes Measurement Information System: Global Health Scale were 0.90 in a midtreatment evaluation at 4 weeks after baseline, 1.76 in a posttreatment evaluation at 8 weeks, and 1.76 at a 24-week follow-up assessment (P less than 0.001 for all comparisons).

Likewise, adjusted differences in the Warwick-Edinburgh Mental Wellbeing Scale were 1.04, 2.68, and 2.95 at 4, 8, and 24 weeks, respectively.

Adjusted differences in the Glasgow Sleep Impact Index, which measures sleep-related quality of life, were –8.76, –17.60, and –18.72 at 4, 8, and 24 weeks, respectively, indicating a benefit of the digital CBT intervention over the control intervention, the investigators said.

About 45%-84% of these effects were attributable to changes in insomnia symptoms, results of a mediation analysis showed.

Insomnia scores as measured by the eight-item SCI scale were 6.5 and 6.6 at baseline for the digital CBT and control groups, respectively. By week 4, SCI scores were 9.96 and 13.00 for the two groups (P less than 0.001), with significant differences also reported at the 8- and 24-week evaluations.

The investigators noted that their findings might not be generalizable because participants were not drawn from patient populations. In addition, although 58% of the participants completed 4 weeks or more of the digital CBT sessions, the dropout rate was “substantial.”

Nevertheless, they wrote, these findings, together with results of a recently reported parallel study looking at the effects of sleep on mental health, affirm CBT as the treatment of choice for insomnia. “The mediation analyses in these two studies, with a total of 5,466 participants, provide novel and convincing evidence that insomnia may be a legitimate and important target for mental health and well-being.”

Dr. Espie reported that he is cofounder and chief medical officer of Big Health. He is a shareholder and receives a salary from the company, which was involved in the design and conduct of the study, interpretation of data, and development of the manuscript appearing in JAMA Psychiatry. The study was funded by Big Health and other sources, including the National Institute for Health Research Oxford Biomedical Research Centre.

SOURCE: Espie CA et al. JAMA Psychiatry. 2018 Sep 25. doi: 10.1001/jamapsychiatry.2018.2745.

Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.

Xavier_S/Thinkstock

Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.

Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.

“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.

The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.

Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.

As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.

Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.

Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.

This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.

Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.

Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.

The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.

SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.

Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.

Xavier_S/Thinkstock

Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.

Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.

“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.

The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.

Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.

As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.

Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.

Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.

This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.

Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.

Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.

The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.

SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.

Bacteremic sepsis during acute lymphoblastic leukemia (ALL) treatment may contribute to neurocognitive dysfunction later in life, results of a cohort study suggest.

Xavier_S/Thinkstock

Pediatric ALL survivors who had sepsis while on treatment performed worse on measures of intelligence, attention, executive function, and processing speed than survivors with no sepsis history, according to study results.

Links between sepsis and impaired neurocognitive function found in this study have “practice-changing implications” for cancer survivors, investigators reported in JAMA Pediatrics.

“Prevention of infection, early recognition and appropriate management of sepsis, and preemptive neurocognitive interventions should be prioritized, because these might prevent or ameliorate neurologic damage,” said Joshua Wolf, MBBS, of St. Jude Children’s Research Hospital, Memphis, and the coauthors of the report.

The study included 212 children who, at a median age of 5 years, had received risk-adapted chemotherapy for ALL with no hematopoietic cell transplant or cranial irradiation.

Sixteen of the patients (7.5%) had a history of bacteremic sepsis during ALL therapy, according to retrospectively obtained data.

As a part of the study, all participants participated in neurocognitive testing, which was done at a median of 7.7 years after diagnosis.

Patients with a history of bacteremic sepsis performed poorly on multiple measures of neurocognitive function, as compared with all other participants, according to results of analyses that were adjusted for multiple potentially confounding factors, such as age, race, and leukemia risk category.

Although not all neurocognitive measures were significantly different between groups, survivors with a sepsis history performed worse on evaluations of spatial planning (difference, 0.78; 95% confidence interval, 0.57-1.00), verbal fluency (0.38; 95% CI, 0.14-0.62), and attention (0.63; 95% CI, 0.30-0.95), among other measures, investigators said.

This is believed to be the first published study looking at potential links between sepsis during ALL treatment and long-term neurocognitive dysfunction, investigators said. However, similar observations have been made in other patient populations, they added.

Exactly how sepsis might lead to neurocognitive deficits remains unclear. “In the population of children with cancer, these mechanisms might be augmented by increased blood-brain barrier permeability to neurotoxic chemotherapy drugs,” they said in their report.

Further study is needed to look at potential brain injury mechanisms, and to validate the current findings in other ALL patient cohorts, they concluded.

The study was supported by the National Institute of Mental Health, the National Cancer Institute, and the American Lebanese Syrian Associated Charities. The researchers reported having no conflicts of interest.

SOURCE: Cheung YT et al. JAMA Pediatr. 2018 Sep 24. doi:10.1001/jamapediatrics.2018.2500.

Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.

Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).

The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.

Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.

“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.

Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.

The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.

Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.

Clinical depression was significantly associated with arthritis, with an odds ratio of 1.21 (95% confidence interval, 1.09-1.34) in a post hoc comparison model that controlled for age, gender, comorbid conditions, and other factors such as smoking history.

Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.

“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.

The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.

The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.

SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.

Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.

Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).

The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.

Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.

“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.

Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.

The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.

Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.

Clinical depression was significantly associated with arthritis, with an odds ratio of 1.21 (95% confidence interval, 1.09-1.34) in a post hoc comparison model that controlled for age, gender, comorbid conditions, and other factors such as smoking history.

Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.

“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.

The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.

The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.

SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.

Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.

Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).

The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.

Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.

“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.

Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.

The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.

Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.

Clinical depression was significantly associated with arthritis, with an odds ratio of 1.21 (95% confidence interval, 1.09-1.34) in a post hoc comparison model that controlled for age, gender, comorbid conditions, and other factors such as smoking history.

Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.

“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.

The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.

The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.

SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Hyperprogressive disease is a new pattern of progression that may be more prevalent in patients with non–small-cell lung cancer receiving treatment with PD-1/PD-L1 inhibitors than in those receiving chemotherapy, results of a multicenter retrospective study suggest.

Nearly 14% of patients treated with PD/1/PD-L1 inhibitors had hyperprogressive disease in the study, compared with about 5% of patients treated with chemotherapy, the investigators reported.

This acceleration of tumor growth during therapy was associated with a high metastatic burden before treatment, and with a poor prognosis after treatment, wrote Benjamin Besse, MD, PhD, of the cancer medicine department at Gustave Roussy, Villejuif, France, and his colleagues.

Based on these findings, disease evolution should be carefully monitored to identify “hyperprogressors” among non–small-cell lung cancer (NSCLC) patients receiving PD-1/PD-L1 inhibitors, Dr. Besse and his colleagues said.

“Because of the poor overall survival associated with hyperprogressive disease, an early switch to salvage chemotherapy in these patients should be considered,” they wrote in JAMA Oncology.

This is believed to be the first study to look at incidence of hyperprogressive disease after PD-1/PD-L1 therapy specifically in NSCLC patients, and the first in any tumor type to include a chemotherapy treatment control group, according to Dr. Besse and his coauthors.

In one other recent report, hyperprogressive disease was seen in 9% of advanced cancers, and in a second recent investigation, it was seen in 29% of head and neck cancer patients, they said.

Although those proportions appear different, that could be due to differing interpretations of hyperprogressive disease, as there is no consensus on the optimal definition, they noted.

In this study, which included 406 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors and 59 treated with chemotherapy, hyperprogressive disease was defined as progressive disease observed at the first computed tomography scan and an absolute increase in tumor growth rate of 50% or more per month.

A total of 56 patients (13.8%) in the PD-1/PD-L1 treatment group met that definition for hyperprogressive disease, the investigators found. By comparison, three patients (5.1%) in the chemotherapy treatment group had hyperprogressive disease.

With a median follow-up of 12.1 months in the PD-1/PD-L1 group, the median overall survival was 13.4 months. Median overall survival for those with progressive disease was 6.2 months, and significantly lower at 3.4 months for those who had experienced hyperprogressive disease (P = .002), Dr. Besse and his coinvestigators found.

Moreover, 42.6% patients with progressive disease had two or more metastatic sites, compared with 62.5% of patients with hyperprogressive disease (P = .006), they reported.

The phenomenon of hyperprogressive disease might explain the initial excess in deaths seen in some phase 3 trials, Dr. Besse said in an interview posted on the JAMA Oncology website.

“In most of the second-line trials that compared single-agent immunotherapy to single-agent chemotherapy, overall survival curves crossed, meaning that there were an extra number of deaths in the immunotherapy arm,” he said in the interview. “That led us to evaluate the speed of progression.”

Based on the study results, Dr. Besse recommends early assessment by CT scan at 6 or 8 weeks after the start of immunotherapy. “If a patient has hyperprogressive disease, you don’t have much time to react,” he said. “You have to switch to a new treatment quite early.”

Dr. Besse reported receiving research funding from AstraZeneca, Boehringer, Bristol-Myers Squibb, Clovis Oncology, GlaxoSmithKline, Eli Lilly, Inivata, Merck Sharp & Dohme, Onxeo, OSE Pharma, Pfizer, Roche/Genentech, and Servier.
 

SOURCE: Ferrara R et al. JAMA Oncol. 2018 Sep 6. doi: 10.1001/jamaoncol.2018.3676.

Hyperprogressive disease is a new pattern of progression that may be more prevalent in patients with non–small-cell lung cancer receiving treatment with PD-1/PD-L1 inhibitors than in those receiving chemotherapy, results of a multicenter retrospective study suggest.

Nearly 14% of patients treated with PD/1/PD-L1 inhibitors had hyperprogressive disease in the study, compared with about 5% of patients treated with chemotherapy, the investigators reported.

This acceleration of tumor growth during therapy was associated with a high metastatic burden before treatment, and with a poor prognosis after treatment, wrote Benjamin Besse, MD, PhD, of the cancer medicine department at Gustave Roussy, Villejuif, France, and his colleagues.

Based on these findings, disease evolution should be carefully monitored to identify “hyperprogressors” among non–small-cell lung cancer (NSCLC) patients receiving PD-1/PD-L1 inhibitors, Dr. Besse and his colleagues said.

“Because of the poor overall survival associated with hyperprogressive disease, an early switch to salvage chemotherapy in these patients should be considered,” they wrote in JAMA Oncology.

This is believed to be the first study to look at incidence of hyperprogressive disease after PD-1/PD-L1 therapy specifically in NSCLC patients, and the first in any tumor type to include a chemotherapy treatment control group, according to Dr. Besse and his coauthors.

In one other recent report, hyperprogressive disease was seen in 9% of advanced cancers, and in a second recent investigation, it was seen in 29% of head and neck cancer patients, they said.

Although those proportions appear different, that could be due to differing interpretations of hyperprogressive disease, as there is no consensus on the optimal definition, they noted.

In this study, which included 406 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors and 59 treated with chemotherapy, hyperprogressive disease was defined as progressive disease observed at the first computed tomography scan and an absolute increase in tumor growth rate of 50% or more per month.

A total of 56 patients (13.8%) in the PD-1/PD-L1 treatment group met that definition for hyperprogressive disease, the investigators found. By comparison, three patients (5.1%) in the chemotherapy treatment group had hyperprogressive disease.

With a median follow-up of 12.1 months in the PD-1/PD-L1 group, the median overall survival was 13.4 months. Median overall survival for those with progressive disease was 6.2 months, and significantly lower at 3.4 months for those who had experienced hyperprogressive disease (P = .002), Dr. Besse and his coinvestigators found.

Moreover, 42.6% patients with progressive disease had two or more metastatic sites, compared with 62.5% of patients with hyperprogressive disease (P = .006), they reported.

The phenomenon of hyperprogressive disease might explain the initial excess in deaths seen in some phase 3 trials, Dr. Besse said in an interview posted on the JAMA Oncology website.

“In most of the second-line trials that compared single-agent immunotherapy to single-agent chemotherapy, overall survival curves crossed, meaning that there were an extra number of deaths in the immunotherapy arm,” he said in the interview. “That led us to evaluate the speed of progression.”

Based on the study results, Dr. Besse recommends early assessment by CT scan at 6 or 8 weeks after the start of immunotherapy. “If a patient has hyperprogressive disease, you don’t have much time to react,” he said. “You have to switch to a new treatment quite early.”

Dr. Besse reported receiving research funding from AstraZeneca, Boehringer, Bristol-Myers Squibb, Clovis Oncology, GlaxoSmithKline, Eli Lilly, Inivata, Merck Sharp & Dohme, Onxeo, OSE Pharma, Pfizer, Roche/Genentech, and Servier.
 

SOURCE: Ferrara R et al. JAMA Oncol. 2018 Sep 6. doi: 10.1001/jamaoncol.2018.3676.

Hyperprogressive disease is a new pattern of progression that may be more prevalent in patients with non–small-cell lung cancer receiving treatment with PD-1/PD-L1 inhibitors than in those receiving chemotherapy, results of a multicenter retrospective study suggest.

Nearly 14% of patients treated with PD/1/PD-L1 inhibitors had hyperprogressive disease in the study, compared with about 5% of patients treated with chemotherapy, the investigators reported.

This acceleration of tumor growth during therapy was associated with a high metastatic burden before treatment, and with a poor prognosis after treatment, wrote Benjamin Besse, MD, PhD, of the cancer medicine department at Gustave Roussy, Villejuif, France, and his colleagues.

Based on these findings, disease evolution should be carefully monitored to identify “hyperprogressors” among non–small-cell lung cancer (NSCLC) patients receiving PD-1/PD-L1 inhibitors, Dr. Besse and his colleagues said.

“Because of the poor overall survival associated with hyperprogressive disease, an early switch to salvage chemotherapy in these patients should be considered,” they wrote in JAMA Oncology.

This is believed to be the first study to look at incidence of hyperprogressive disease after PD-1/PD-L1 therapy specifically in NSCLC patients, and the first in any tumor type to include a chemotherapy treatment control group, according to Dr. Besse and his coauthors.

In one other recent report, hyperprogressive disease was seen in 9% of advanced cancers, and in a second recent investigation, it was seen in 29% of head and neck cancer patients, they said.

Although those proportions appear different, that could be due to differing interpretations of hyperprogressive disease, as there is no consensus on the optimal definition, they noted.

In this study, which included 406 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors and 59 treated with chemotherapy, hyperprogressive disease was defined as progressive disease observed at the first computed tomography scan and an absolute increase in tumor growth rate of 50% or more per month.

A total of 56 patients (13.8%) in the PD-1/PD-L1 treatment group met that definition for hyperprogressive disease, the investigators found. By comparison, three patients (5.1%) in the chemotherapy treatment group had hyperprogressive disease.

With a median follow-up of 12.1 months in the PD-1/PD-L1 group, the median overall survival was 13.4 months. Median overall survival for those with progressive disease was 6.2 months, and significantly lower at 3.4 months for those who had experienced hyperprogressive disease (P = .002), Dr. Besse and his coinvestigators found.

Moreover, 42.6% patients with progressive disease had two or more metastatic sites, compared with 62.5% of patients with hyperprogressive disease (P = .006), they reported.

The phenomenon of hyperprogressive disease might explain the initial excess in deaths seen in some phase 3 trials, Dr. Besse said in an interview posted on the JAMA Oncology website.

“In most of the second-line trials that compared single-agent immunotherapy to single-agent chemotherapy, overall survival curves crossed, meaning that there were an extra number of deaths in the immunotherapy arm,” he said in the interview. “That led us to evaluate the speed of progression.”

Based on the study results, Dr. Besse recommends early assessment by CT scan at 6 or 8 weeks after the start of immunotherapy. “If a patient has hyperprogressive disease, you don’t have much time to react,” he said. “You have to switch to a new treatment quite early.”

Dr. Besse reported receiving research funding from AstraZeneca, Boehringer, Bristol-Myers Squibb, Clovis Oncology, GlaxoSmithKline, Eli Lilly, Inivata, Merck Sharp & Dohme, Onxeo, OSE Pharma, Pfizer, Roche/Genentech, and Servier.
 

SOURCE: Ferrara R et al. JAMA Oncol. 2018 Sep 6. doi: 10.1001/jamaoncol.2018.3676.

Photo from Penn Medicine

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but the treatment should only be used in patients expected to derive the most benefit, according to new guidelines from the International Lymphoma Radiation Oncology Group.

The guidelines note that proton therapy reduces the radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart.

However, the advantages of proton therapy are not always clear in other situations, such as when the target spans the right side of the heart or when the target is above the heart with no axillary involvement.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” said guideline author Bouthaina Dabaja, MD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues.

The group’s guidelines were published in Blood.

The guidelines note that proton therapy—like intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy—presents an opportunity for more conformal dose distribution and better sparing of organs at risk.

Proton therapy can greatly benefit certain patients with mediastinal disease, including:

• Young female patients in whom proton therapy would reduce the breast dose and decrease the risk of secondary breast cancer
• Patients at high risk of radiation-related toxicity due to previous treatment
• Patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines.

However, the consideration of proton therapy needs to factor in the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy is the least complex delivery technique, it is challenging because beams can conform only to one side of the target. In contrast, active mode pencil beam scanning proton therapy potentially provides better conformality and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said.

However, “motion management is of prime importance” with pencil beam scanning proton therapy, which is more sensitive to density changes in the beam path than is passive scattering proton therapy.

To that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

Dr. Dabaja and her coauthors reported no funding or conflicts of interest.

Photo from Penn Medicine

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but the treatment should only be used in patients expected to derive the most benefit, according to new guidelines from the International Lymphoma Radiation Oncology Group.

The guidelines note that proton therapy reduces the radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart.

However, the advantages of proton therapy are not always clear in other situations, such as when the target spans the right side of the heart or when the target is above the heart with no axillary involvement.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” said guideline author Bouthaina Dabaja, MD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues.

The group’s guidelines were published in Blood.

The guidelines note that proton therapy—like intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy—presents an opportunity for more conformal dose distribution and better sparing of organs at risk.

Proton therapy can greatly benefit certain patients with mediastinal disease, including:

• Young female patients in whom proton therapy would reduce the breast dose and decrease the risk of secondary breast cancer
• Patients at high risk of radiation-related toxicity due to previous treatment
• Patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines.

However, the consideration of proton therapy needs to factor in the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy is the least complex delivery technique, it is challenging because beams can conform only to one side of the target. In contrast, active mode pencil beam scanning proton therapy potentially provides better conformality and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said.

However, “motion management is of prime importance” with pencil beam scanning proton therapy, which is more sensitive to density changes in the beam path than is passive scattering proton therapy.

To that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

Dr. Dabaja and her coauthors reported no funding or conflicts of interest.

Photo from Penn Medicine

Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but the treatment should only be used in patients expected to derive the most benefit, according to new guidelines from the International Lymphoma Radiation Oncology Group.

The guidelines note that proton therapy reduces the radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart.

However, the advantages of proton therapy are not always clear in other situations, such as when the target spans the right side of the heart or when the target is above the heart with no axillary involvement.

“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” said guideline author Bouthaina Dabaja, MD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues.

The group’s guidelines were published in Blood.

The guidelines note that proton therapy—like intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy—presents an opportunity for more conformal dose distribution and better sparing of organs at risk.

Proton therapy can greatly benefit certain patients with mediastinal disease, including:

• Young female patients in whom proton therapy would reduce the breast dose and decrease the risk of secondary breast cancer
• Patients at high risk of radiation-related toxicity due to previous treatment
• Patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.

“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines.

However, the consideration of proton therapy needs to factor in the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.

While passive scattering proton therapy is the least complex delivery technique, it is challenging because beams can conform only to one side of the target. In contrast, active mode pencil beam scanning proton therapy potentially provides better conformality and sparing of organs at risk.

“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said.

However, “motion management is of prime importance” with pencil beam scanning proton therapy, which is more sensitive to density changes in the beam path than is passive scattering proton therapy.

To that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.

Dr. Dabaja and her coauthors reported no funding or conflicts of interest.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.

follicular lymphoma

A subset of follicular lymphoma (FL) patients managed with watchful waiting are vulnerable to organ dysfunction and transformation, according to research published in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study, about 24% of FL patients managed with watchful waiting developed significant organ dysfunction or transformation at first progression over 8.2 years of follow-up.

Organ dysfunction and transformation were associated with significantly worse overall survival (OS) that could not be predicted based on baseline characteristics.

Gwynivere A. Davies, MD, of the University of Calgary in Alberta, Canada, and her colleagues conducted this study using  data from the Alberta Lymphoma Database. The team gathered data on patients with grade 1-3a FL who were diagnosed between 1994 and 2011.

The investigators identified 238 patients who were initially managed with watchful waiting. The patients had a median age of 54.1 years (range, 24.7-69.9) at diagnosis, and 83.2% were advanced stage.

The 10-year OS rate for these patients was 81.2%. At a median follow-up of 98.5 months, 71% (n=169) of patients had progressed and required therapy.

At the time of progression, 24.4% of patients (n=58) had organ dysfunction and/or transformation. The median time to organ dysfunction/transformation was 29.9 months.

These adverse outcomes were significantly associated with inferior OS. The 10-year OS rate was 65.4% for patients with transformation at progression and 83.2% for those without transformation (P=0.0017).

The 10-year OS rate was 71.5% for those with organ dysfunction at progression and 82.7% for those without organ dysfunction (P=0.028).

Comparison to treated patients

The investigators also looked at a comparison group of 236 FL patients managed with immediate rituximab-based chemotherapy (R-chemo), most of whom were scheduled to receive (72.9%) rituximab maintenance. Their median age was 52.1 (range, 27.3-65.4), and most (82.6%) had advanced stage disease.

At a median follow-up of 100.2 months, the median progression-free survival (PFS) was not reached. The 10-year OS rate was 84%.

The 10-year PFS rate after first R-chemo was 57.1% for patients who received immediate R-chemo (n=236) and 50.5% for patients who were initially managed with watchful waiting and proceeded to R-chemo (n=133; P=0.506). This was not affected by rituximab maintenance.

The investigators noted that OS measured from diagnosis was not affected by initial watchful waiting.

However, in a landmark analysis, OS was inferior when measured from R-chemo at first progression for watchful waiting recipients compared to patients who received immediate R-chemo. The 10-year OS rates were 74.4% and 84.0%, respectively (P=0.02).

The risk of transformation at first progression was significantly different between the groups. At 10 years, the rate of transformation was 25.5% in the watchful waiting group and 6.3% in the immediate R-chemo group (P<0.0001).

The investigators said these findings, taken together, suggest changes may be warranted for FL patients managed with watchful waiting.

“Consideration should be given to implementing standardized follow-up imaging, with early initiation of rituximab-based therapy if there is evidence of progression in an attempt to prevent these potentially clinically impactful events [i.e., organ dysfunction and transformation],” Dr. Davies and her coauthors wrote.

Dr. Davies reported no financial disclosures. Her coauthors reported disclosures related to Janssen, Gilead Sciences, Lundbeck, Roche, AbbVie, Amgen, Seattle Genetics, Bristol-Myers Squibb, Servier Laboratories, and Merck.