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Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
Newer targeted drugs for chronic lymphocytic leukemia also appear to have a beneficial impact on underlying autoimmune cytopenias (AICs), results of a large retrospective study suggest.
Many autoimmune cytopenias improved or resolved during treatment with ibrutinib, idelalisib, or venetoclax, according to authors of the study, which appears in the journal Blood.
Treatment-emergent autoimmune cytopenias were seen in a “negligible portion” of patients overall, according to the report. The prevalence was about 1% each for patients treated with ibrutinib or idelalisib, though seen more frequently (at 7%) among patients who received venetoclax.
Nevertheless, treatment-emergent autoimmune cytopenias were “easily manageable” without interventions such as steroids and rituximab, and without need to interrupt the targeted treatment for chronic lymphocytic leukemia (CLL), according to the authors, led by Candida Vitale, MD, PhD, of the department of molecular biotechnology and health sciences at the University of Torino in Italy.
“Ibrutinib, idelalisib, and venetoclax have a beneficial impact on CLL-related preexisting AICs, achieving in most patients, in parallel with the consolidated antitumor efficacy, an effective control of the autoimmune phenomena,” Dr. Vitale and coauthors wrote in their report.
Study results
The retrospective study included 815 patients, of whom 572 were treated with ibrutinib, 143 with idelalisib plus rituximab, and 100 with venetoclax. Nine percent of ibrutinib-treated patients and 12% of venetoclax-treated patients also received an anti-CD20 monoclonal antibody, rituximab or obinutuzumab.
One hundred and four patients (13%) had preexisting autoimmune cytopenias, though the majority were resolved or controlled at the time targeted therapy was started.
Of patients with autoimmune cytopenias that were unresolved at the beginning of targeted therapy, 80% improved or resolved after starting targeted treatment, authors reported.
Most patients who developed autoimmune cytopenias on treatment had high-risk features such as unmutated IGHV, del(17)p, or TP53 mutation, according to the report.
Those treatment-emergent autoimmune cytopenias were seen in 1% of the ibrutinib group, 0.9% of the idelalisib group, and 7% of the venetoclax group. Out of 12 total treatment-emergent autoimmune cytopenias, all but 2 were resolved or controlled with dose reductions or temporary suspensions and use of steroids or rituximab, the report shows.
The higher incidence of autoimmune cytopenias in the venetoclax group held steady even when considering just the patients who had relapsed/refractory disease or had at least two prior lines of therapy, suggesting a “more meaningful” incidence, compared to what was observed for ibrutinib and idelalisib, the investigators said.
“However, the risk of autoimmune cytopenia episodes should not limit the use of venetoclax, considering the strong efficacy of this drug in treating patients with CLL, including those with high-risk features, and the possibility of effectively managing autoimmune complications, mostly without treatment interruption,” they concluded in their report.
Implications for patients with CLL
Findings of this study indicate that targeted therapies are effective for managing both CLL and autoimmune cytopenias, according to Carol Moreno, MD, PhD, of Hospital Sant Pau in Barcelona.
Moreover, the targeted therapies do not appear to change the overall prevalence of autoimmune cytopenias, compared to untreated patients, Dr. Moreno said in a commentary on the findings also published in Blood.
“These results are consistent with the concept that targeted therapies are not associated with a higher risk of autoimmune cytopenias, and that, if present, can be managed with immunosuppressive agents,” she wrote.
Autoimmune cytopenias and CLL
Autoimmune cytopenias are a relatively common complication of CLL, occurring in 5%-9% of CLL patients, Dr. Vitale and coauthors said in their report. The most common presentations include autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP).
Evidence from earlier studies suggests that treatment for CLL may trigger autoimmune cytopenias. Results of retrospective studies in the 1990s linked single-agent fludarabine to increased risk of AIHA, Dr. Moreno said in the commentary.
However, subsequent studies showed that fludarabine plus cyclophosphamide (FC) and fludarabine, cyclophosphamide, and rituximab (FCR) were associated with low proportions of AIHA.
“Taken together, these results convincingly suggest that rather than treatment, it is the lack of response to it that conveys a higher risk of AIC,” Dr. Moreno wrote.
Management considerations
There are currently no clinical practice guidelines that advise on how to manage patients who develop AICs during targeted treatment for CLL, Dr. Vitale and colleagues said in their report.
However, this new study data may help inform management of patients with CLL and an autoimmune cytopenia, Dr. Moreno said in the commentary.
If the patient doesn’t immediately require CLL treatment, patients can be managed according to existing guidelines for AIHA and ITP, she said. “Nonresponding patients should be given CLL therapy,” she added.
For CLL patients who do require therapy and have a preexisting or treatment-emergent AIC, a “CLL-oriented” treatment approach could be considered, according to Dr. Moreno.
“A reasonable approach consists of a short course (2 to 4 weeks) of corticosteroids followed by effective CLL therapy (i.e., FCR, bendamustine plus rituximab or ibrutinib), depending on the clinical situation,” she added.
Dr. Vitale reported receiving consultancy fees from Janssen outside the submitted work. Dr. Moreno declared no competing financial interests related to her commentary.
FROM BLOOD
