Duvelisib combos show promise for PTCL, CTCL

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.

Photo by Larry Young

LA JOLLA, CA—Phase 1 results suggest duvelisib combination therapies can be active and well-tolerated in patients with relapsed/refractory T-cell lymphomas.

Researchers said duvelisib had an acceptable safety profile when given in combination with romidepsin or bortezomib to patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL).

Duvelisib plus romidepsin produced a 60% overall response rate (ORR) in these patients, and duvelisib plus bortezomib produced a 35% ORR.

Response rates were higher in PTCL patients than CTCL patients.

Neha Mehta-Shah, MD, of Washington University in St. Louis, Missouri, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum.

The research was supported by the Leukemia & Lymphoma Society, Infinity Pharmaceuticals, and Verastem Inc.

This phase 1 trial consists of parallel arms evaluating duvelisib in combination with romidepsin (arm A) or bortezomib (arm B). The trial enrolled patients with PTCL or CTCL that had progressed after at least 1 prior therapy.

All patients received duvelisib at 25 mg, 50 mg, or 75 mg twice daily for 28-day cycles.

Patients in arm A received romidepsin at 10 mg/m² on days 1, 8, and 15 of each cycle.

Patients in arm B received bortezomib at 1 mg/m² on days 1, 4, 8, and 11 of each cycle.

Romidepsin combination

Sixteen patients received duvelisib plus romidepsin, and 15 of them were evaluable for efficacy. Eleven patients had PTCL, and 4 had CTCL.

The ORR was 60% (9/16), and the complete response (CR) rate was 27% (n=4). The median time to response was 51 days (range, 49-54).

The ORR was 64% in the PTCL patients and 50% in the CTCL patients. All 4 CRs occurred in PTCL patients, 2 in patients with PTCL not otherwise specified (NOS) and 2 in patients with angioimmunoblastic T-cell lymphoma (AITL).

There were 5 responses among patients who received the 75 mg dose of duvelisib (n=8) and 2 responses each in the 50 mg dose group (n=3) and 25 mg dose group (n=4).

There were no dose-limiting toxicities, so the 75 mg dose of duvelisib was considered the maximum tolerated dose.

All 16 patients were evaluable for safety. There were 2 serious adverse events (AEs) considered possibly related to treatment—grade 3 fatigue and grade 2 aspartate aminotransferase (AST) increase.

There were 2 deaths considered unrelated to treatment—diffuse alveolar hemorrhage after allogeneic transplant and sepsis in the setting of disease progression.

Treatment-related AEs (occurring in at least 2 patients) were fatigue (56%), nausea (50%), altered taste (50%), diarrhea (38%), neutropenia (38%), rash (31%), thrombocytopenia (25%), dysphagia (25%), and anorexia (25%).

Grade 3/4 treatment-related AEs included neutropenia (38%) and thrombocytopenia (6%).

One patient discontinued duvelisib-romidepsin due to toxicity, and 7 discontinued due to progressive disease.

Three patients proceeded to bone marrow transplant/donor lymphocyte infusion, and 4 patients are still receiving study treatment.

Bortezomib combination

There were 17 patients who received duvelisib plus bortezomib—10 with PTCL and 7 with CTCL.

The ORR was 35% (6/17), and the CR rate was 18% (n=3). The median time to response was 52 days (range, 47-57).

The ORR was 50% in PTCL patients and 14% among CTCL patients.

All 3 CRs occurred in the PTCL patients—1 in a patient with AITL, 1 in a patient with PTCL-NOS, and 1 in a patient who had intestinal T-cell lymphoma with B-cell lymphoproliferative disorder.

There were 3 responses among patients who received the 25 mg dose of duvelisib (n=8), 2 responses in the 50 mg dose group (n=3), and 1 response in the 75 mg dose group (n=6).

There was 1 dose-limiting toxicity—pneumonia—in a patient treated at the 25 mg dose.

The 25 mg dose was deemed optimal due to grade 3 alanine transaminase (ALT)/AST elevations observed after cycle 1 with the 50 mg dose (n=3) and the 75 mg dose (n=2).

There were 6 serious AEs considered possibly related to treatment:

• Grade 3 pneumonia (n=2)
• Grade 3 infectious colitis (n=1)
• Grade 3 colitis (n=1)
• Grade 4 ALT/AST elevation (n=1)
• Grade 5 Stevens-Johnson syndrome (n=1).

The fatal case of Stevens-Johnson syndrome was considered possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was started at the beginning of the study.

Treatment-related AEs (occurring in at least 2 patients) included diarrhea/colitis (71%), ALT/AST increase (41%), rash (24%), neutropenia (24%), nausea/vomiting (24%), chills (24%), fatigue (24%), and alkaline phosphatase increase (12%).

Grade 3/4 AEs included ALT/AST increase (35%), rash (12%), neutropenia (12%), diarrhea/colitis (6%), and alkaline phosphatase increase (6%).

Seven patients discontinued duvelisib-bortezomib due to toxicity, and 8 discontinued due to disease progression. Two patients are still on study treatment.