Immunotherapy proves active against MF, SS

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.

Youn Kim, MD

Photo by Larry Young

SAN FRANCISCO—The PD-1-blocking antibody pembrolizumab can produce “significant objective clinical responses” in patients with relapsed or refractory cutaneous T-cell lymphoma, according to researchers.

The drug elicited partial responses in 33% of patients enrolled in a phase 2 study. Half of the responders had mycosis fungoides (MF), and half had Sézary syndrome (SS).

All responses are ongoing, and a few patients with stable disease remain on treatment, so they may convert to partial responses, according to Youn Kim, MD, of Stanford University School of Medicine in California.

Dr Kim presented this research at the 8th Annual T-cell Lymphoma Forum.

The study was conducted by the Cancer Immunotherapy Trials Network (CITN) and supported by the National Cancer Institute and Merck, the company developing pembrolizumab.

“There’s good rationale for immune checkpoint blockade in [MF and SS],” Dr Kim said. “There’s systemic and local immune impairment in MF and Sézary, and there’s mounting evidence that T-cell immunity is critical for meaningful antitumor response.”

“[T]umor-infiltrating CD8+ T cells [have been] associated with improved survival, and therapies which augment T-cell function are effective in [MF and SS]. PD-1 and PD-L1 are very well expressed in the tissue and blood, [and] there’s good genomic evidence of immune evasion in [MF and SS].”

With all this in mind, Dr Kim and her colleagues conducted their phase 2 trial of pembrolizumab in 24 patients with relapsed or refractory MF/SS. Patients were excluded if they had central nervous system disease, autoimmune disease, immunodeficiency, or had received immunosuppressive therapy within 7 days.

The patients’ median age was 67 (range, 44-85), and most were male (75%). Thirty-eight percent of patients (n=9) had MF, and 62% (n=15) had SS. Twelve percent (n=3) had large-cell transformation.

Most patients had Stage IVA disease (62%, n=15), followed by IIIB (13%, n=3), IIIA (13%, n=3), IIB (8%, n=2), and IB (4%, n=1). The median number of prior systemic therapies was 4 (range, 1-10).

Treatment and response

Patients received pembrolizumab at 2 mg/kg intravenously every 3 weeks and were allowed to continue therapy for up to 2 years. Dr Kim noted that patients could continue treatment even after the initial documentation of progressive disease (PD) due to the possibility of immune-mediated flare reactions.

“So it’s the investigator’s decision to allow treatment beyond the initial PD,” she said. “However, if there’s confirmation of PD, those people will be removed.”

The median follow-up was 21 weeks (range, 7-39). Eight patients responded to treatment (according to global response criteria), all of which were partial responses. Four of the responders had MF, and 4 had SS. Responses occurred across all disease stages except IB.

“The range of prior therapies varied in the responders,” Dr Kim noted. “People think [patients tend to respond to] immunotherapy [if they are only] mildly [pre-]treated, but that was not the case. Heavily treated patients had great responses to pembrolizumab.”

All responses are ongoing, with a median duration of 13+ weeks (range, 3+ to 30+). The median time to response was 11 weeks (range, 8-22).

Dr Kim noted that 1 responder discontinued treatment because of a severe adverse event, but this patient remains in response without having received subsequent treatment.

The median best mSWAT (modified Skin Weighted Assessment Tool) reduction was 16%. Two patients had near-complete responses in the skin, and 2 patients with stable disease in the skin continue to improve.

Eleven of the 15 SS patients had measurable Sézary burden pre-treatment. And 3 of these patients had a greater than 50% reduction in Sézary count after treatment.

Four patients with stable disease are still on treatment. And at 20 weeks, 75% of patients are progression-free, according to Kaplan-Meier estimates.

Adverse events

Drug-related adverse events occurring at least twice included skin eruptions (21%, n=5), anemia (13%, n=3), decrease in white blood cell count (8%, n=2), elevated liver tests (8%, n=2), diarrhea (8%, n=2), fever (8%, n=2), and face edema (8%, n=2).

Grade 3/4 adverse events included skin eruptions (8%, n=2), anemia (8%, n=2), elevated liver tests (4%, n=1), and face edema (4%, n=1). Skin eruptions (of all grades) included exfoliative dermatitis (n=2), immune-mediated skin flare (n=2), and excessive peeling/edema (n=1).

There were no drug-related serious adverse events. The cause of the aforementioned serious adverse event (which prompted the responding patient to discontinue treatment) could not be determined.

There were 4 patients who did not report any adverse events, regardless of attribution.

In closing, Dr Kim said it is important to conduct biomarker correlative studies to understand the tumor escape mechanisms and enrich the response population.

She and her colleagues at CITN are now exploring the use of pembrolizumab in combination therapy. They are considering combining the drug with interferon-gamma, interleukin-12, low-dose total skin radiation, intratumoral ipilimumab, or Toll-like receptor agonists.