First PD Inhibitor in Hematology: Nivolumab for Lymphoma

Zosia Chustecka

Disclosures

May 18, 2016

For the first time, an immunotherapy acting on the programmed cell death (PD) pathway has been approved for use in a hematological malignancy.

Nivolumab (Opdivo, Bristol-Myers Squibb) is already approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma. In all of these tumor types, the immunotherapy has shown an improvement in survival when compared with conventional chemotherapy.

Now the US Food and Drug Administration has granted the drug an accelerated approval, based on overall response rate, for use in certain patients with classical Hodgkin's lymphoma. These are patients who have relapsed or progressed after undergoing an autologous hematopoietic stem cell transplantation (auto-HSCT) and are receiving post-transplantation treatment with brentuximab vedotin (Adcetris, Seattle Genetics).

"It is important to have new treatment options for patients with difficult-to-treat diseases who have exhausted the current available options. Because of the unique pathology and biology of classical Hodgkin's lymphoma, it makes sense from a scientific standpoint to investigate a PD-1 inhibitor," Anas Younes, MD, medical oncologist and chief of lymphoma service, Memorial Sloan Kettering Cancer Center, New York City, said in a statement.

"The recent clinical data with nivolumab in patients with classical Hodgkin's lymphoma who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin are encouraging and have the potential to impact our approach to treating these individuals in the future," Dr Younes commented.

Details of the Response Rates

The accelerated approval was granted on the basis of a combined analysis of data from the phase 2 CheckMate 205 (n = 240) and the phase 1 CheckMate 039 (n = 23) trials, according to the manufacturer.

Patients received single-agent nivolumab 3 mg/kg as an intravenous infusion over 60 minutes every 2 weeks until disease progression, maximal clinical benefit, or unacceptable toxicity. Patients received a median of 17 doses of nivolumab (range, 3 - 48), with a median duration of therapy of 8.3 months (range, 1.9 - 24.0 months).

The efficacy analysis was conducted on data from 95 patients who had participated in the two studies.

The objective response rate, assessed by an independent radiographic review committee, was 65% (95% confidence interval [CI], 55 - 75; 62/95 patients), the company noted.

Complete responses were reported in 7% of patients (95% CI, 3 - 15; 7/95 patients), and partial responses in 58% (95% CI, 47 - 68; 55/95 patients). Among responders, the duration of response was maintained over time for a median of 8.7 months (95% CI, 6.8 to not evaluable; range, 0.0+ to 23.1+).

The safety of nivolumab in classical Hodgkin's lymphoma was evaluated in all of the 263 patients who participated in both trials, the company noted. Serious adverse reactions occurred in 21% of patients. The most frequent serious adverse reactions reported in at least 1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis. Ten patients died from causes other than disease progression, including six who died from complications of allogeneic HSCT. In the safety population, 4.2% discontinued treatment because of adverse reactions and 23% of patients had a dose delay for an adverse reaction.

In the subset of patients in the efficacy population (n = 95), serious adverse reactions occurred in 27% of the patients. The most common adverse reactions in these patients were rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%).

In the CheckMate 205 and 039 trials, among all patients (safety population, n = 263) and the subset of patients in the efficacy population (n = 95), respectively, the most common adverse reactions (reported in at least 20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%).

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