Treatment with the CD79b-directed antibody drug conjugate polatuzumab vedotin, when combined with obinutuzumab and lenalidomide, was associated with high rates of complete response (CR) in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase Ib/II trial presented at the 2019 American Society of Clinical Oncology Annual Meeting. The safety profile of this combination also was consistent with the known safety profiles of the individual drugs.
“We were pleasantly surprised by the tolerability of the therapy, as well as its activity,” study presenter and lead author Catherine Diefenbach, MD, of NYU Langone Health, told ASH Clinical News. “I think we need to wait and see what the response signal is for the full efficacy-evaluable population and how durable the progression-free survival (PFS) is with longer follow-up.”
(Editor’s note: On June 10, 2019, the U.S. Food and Drug Administration approved polatuzumab vedotin-piiq in combination with bendamustine and rituximab to treat adults with relapsed or refractory diffuse large B-cell lymphoma who had received at least two prior therapies.)
The open-label, single-arm trial enrolled patients with relapsed/refractory FL: 52 people were included in the safety analysis (median age = 62 years; range = 32-87 years), and 18 were included in the efficacy analysis (median age = 58 years; range = 53-68 years).
In the entire population, participants had received a median of three prior therapies (range = 1-7), half of whom had disease that was refractory to the last treatment. Approximately half of patients had high-risk disease (defined as FL International Prognostic Index score ≥3).
Per study protocol, patients received induction treatment with six 28-day cycles of:
- obinutuzumab 1,000 mg on days 1, 8, and 15 of cycle 1, then day 1 of cycles 2-6
- polatuzumab 1.4 mg/kg or 1.8 mg/kg on day 1 of each cycle
- lenalidomide 10-20 mg on days 1-21 of each cycle
At the end of induction, patients who experienced a CR, partial response (PR), or stable disease continued to receive maintenance therapy with obinutuzumab 1,000 mg every two months for up 24 months, plus lenalidomide 10 mg monthly for 12 months.
At the time of data cutoff (July 6, 2018), all patients experienced at least one adverse event (AE) and 39 (75%) experienced a grade 3-4 AE. The most common grade ≥3 AEs included:
- neutropenia (46%)
- thrombocytopenia (17%)
- anemia (12%)
- infections (12%)
Eight patients (15%) discontinued any drug due to AEs. In addition, one patient experienced a grade 5 AE (septic shock following progressive disease).
After a median follow-up of 16.6 months (range = 3.2-25.1 months), response rates were “promising,” she added. Fourteen of the 18 efficacy-evaluable patients (78%) experienced a CR and two patients (11%) achieved a PR, per Lugano 2014 criteria, for an objective response rate of 89%.
According to the interim analysis, the median PFS was not reached (range not reported) and the 12-month PFS rate was 90%. Two of the 17 responders have experienced disease progression, while “the remaining patients have ongoing responses, with the longest response lasting for more than 21 months,” the researchers noted.
However, Dr. Diefenbach noted that the implications of these findings are limited by the relatively short follow-up of the study. “Given that rituximab and lenalidomide were recently approved for relapsed FL based on the MAGNIFY and AUGMENT trials with a lower CR rate, I think a lot will depend on how these data look in a few months, particularly the PFS for responding patients.” The trial also is limited by its single-arm design and small patient population.
The authors report relationships with Roche, which sponsored the study.
Diefenbach C, Kahl B, Banerjee L, et al. Polatuzumab vedotin (Pola) + obinutuzumab (G) and lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL): Interim analysis of a phase Ib/II trial. Abstract #7505. Presented at the 2019 American Society of Clinical Oncology Annual Meeting, June 4, 2019; Chicago, Illinois.