Nivolumab produces ‘dramatic’ responses in HL
Photo courtesy of UCLA
LUGANO—The PD-1 checkpoint inhibitor nivolumab produces rapid, durable, and, in some cases, “dramatic” responses in Hodgkin lymphoma (HL), according to a speaker at the 13th International Congress on Malignant Lymphoma.
The drug has also produced durable responses in follicular lymphoma (FL), cutaneous T-cell lymphoma (CTCL), and peripheral T-cell lymphoma (PTCL), although patient numbers for these malignancies are small.
John Timmerman, MD, of the University of California, Los Angeles, presented these results from a phase 1 study of patients with relapsed or refractory lymphoid malignancies and chronic HL (abstract 010).
Bristol-Myers Squibb and Ono Pharmaceutical Company are sponsors of the trial.
Original results of the study, with a data cutoff of June 2014, were reported at ASH 2014, with 40 weeks of median follow-up.
The update presented at 13-ICML, with a data lock in April 2015, includes an additional 10 months of data, for a median follow-up of 76 weeks.
Investigators enrolled 105 patients in this dose-escalation study to receive nivolumab at 1 mg/kg, then 3 mg/kg, every 2 weeks for 2 years.
Twenty-three patients had HL. Thirty-one had B-cell non-Hodgkin lymphoma (NHL), including 11 with FL and 10 with diffuse large B-cell lymphoma (DLBCL).
Twenty-three patients had T-cell NHL, including 5 with PTCL and 13 with CTCL/mycosis fungoides (MF). Twenty-seven patients had multiple myeloma (MM), and 1 had chronic myeloid leukemia.
Patients were heavily pretreated. Seventy-eight percent of HL patients and 26% of T-NHL patients had prior brentuximab vedotin. And 78% (HL), 14% (B-NHL), 9% (T-NHL), and 56% (MM) of patients had a prior autologous transplant.
The median number of prior therapies was 5 (range, 2-15) for HL patients and ranged from 1 to 16 for all patients.
The study’s primary endpoint was safety and tolerability, and the secondary endpoint was efficacy.
Safety and tolerability
Ninety-seven percent of patients had an adverse event, 69% of them related to study treatment and 21% of them treatment-related grade 3-4 events.
Fifteen patients (14%) discontinued treatment due to a related adverse event, including 3 with pneumonitis and 1 each with enteritis, stomatitis, pancreatitis, rash, conjunctivitis, sepsis, diplopia, myositis, neutropenia, myelodysplastic syndrome, increased creatinine phosphokinase, and peripheral neuropathy.
“Immune-related adverse events were generally seen early on and generally of low grade,” Dr Timmerman said. “However, it is notable that there were several grade 3 immune-related adverse events that can be seen as far as 6 months out after the start of therapy.”
These included skin, gastrointestinal, and pulmonary events. Most immune-related adverse events (83%) were resolved using protocol-prescribed procedures.
Efficacy
The overall response rate was 87% for HL, 36% for DLBCL, 40% for FL, 15% for CTCL/MF, 40% for PTCL, and 4% for MM.
Dr Timmerman pointed out that, since ASH, 2 additional conversions from partial response (PR) to complete response (CR) occurred in patients with HL. To date, 6 of 23 HL patients have achieved a CR and 14 a PR.
In B-cell NHL, there were additional conversions from PR to CR in DLBCL, while responses remained the same in FL and in the 4 responders with T-cell lymphomas.
“Intriguingly, there has been 1 late CR in the multiple myeloma cohort, which previously had shown no responses,” Dr Timmerman said.
Durability of response
This study suggests PD-1 blockade can produce durable responses in hematologic malignancies, as it does in melanoma and renal cell carcinoma.
In HL, the median response duration at a median follow-up of 86 weeks has not yet been reached, and half (n=10) of the responses are still ongoing.
