Triplet Regimen Induces High Rate of CR in R/R Follicular Lymphoma

Catherine Diefenbach, MD

The combination of polatuzumab-vedotin (Polivy), obinutuzumab (Gazyva), and lenalidomide (Revlimid) induced a high rate of durable responses in patients with relapsed/refractory follicular lymphoma, according to results presented at the 2019 ASH Annual Meeting.

Catherine Diefenbach, MD, director of the clinical lymphoma program at NYU Langone Health’s Perlmutter Cancer Center, reported response by both the Lugano 2014 criteria and the modified Lugano 2014 criteria. By the modified criteria, the investigator-assessed response rate was 83%, decreasing to 76% by independent review. CR was 61% and 63%, respectively. By the original Lugano criteria, 83% of patients had investigator-assessed objective responses and 76% by independent review. Complete response rates were 74% and 72%, respectively.

The 12-month progression-free survival (PFS) was 83%.

“Our study of the novel triplet combination demonstrates a safety profile consistent with the know profiles of the individual drugs,” Diefenbach, MD, said. “The first report of the full efficacy population showed high complete response rates at the end of induction therapy in a heavily pretreated and refractory population, which compares favorably with currently available therapies for relapsed and refractory follicular lymphoma.”

A subgroup analysis showed an objective response rate (ORR) of 55% and a complete response (CR) of 45% in patients whose disease progressed within 24 months during first-line therapy and 83% and 80%, respectively in patients who had no progression after 24 months. Patients with FLIPI low (0-2) disease had an 85% ORR, including CR in 75%, compared with an ORR of 70% in the FLIPI high subgroup. All responses in the FLIPI high cohort were complete responses.

Additional response analyses showed an ORR of 68% for patients who were refractory to their last line of therapy and 86% for those who were not refractory. ORR was 77% for those who underwent 1 or 2 prior lines of therapy versus 75% for patients who underwent ≥3 lines of therapy.

“These compelling findings support further investigation in a larger patient population as this novel triplet combination has a potential place as therapy for patients with relapsed and refractory follicular lymphoma,” Diefenbach said.

After a median follow-up duration of 15.1 months, the data remain immature for calculating the median PFS, she added.

The trial design included a dose-escalation phase that identified the recommended phase II dosing of 1.4 mg/kg polatuzumab vedotin, 20 mg lenalidomide, and 1000 mg obinutuzumab. Induction consisted of day 1 dosing of polatuzumab vedotin for six 28-day cycles, obinutuzumab on days 1 of the first cycle and then days 1, 8, and 15 on cycles 2 through 6, and lenalidomide on days 1 to 21 of each cycle.

Patients who attained an objective response or stable disease continued treatment with obinutuzumab for a maximum of 24 months and lenalidomide for 12 months. After excluding 10 patients who did not receive the recommended phase II dosing, 46 patients remained for the efficacy analysis, 39 of whom completed the induction phase.

The median age was 62 years, and men accounted for 59% of the total population. Diefenbach reported that 88% of patients had Ann Arbor Stage III/IV disease, 16% had bulky disease, 43% had bone marrow involvement, and 55% had FLIPI high ≥3 disease.

Patients had received a median of 3 prior lines of therapy, 59% were refractory to the last prior therapy, 71% were refractory to any anti-CD20 therapy, and 25% had disease progression within 24 months on first-line therapy.

Thirty-one of fifty-six (55%) patients experienced grade 3/4 neutropenia. The second most common adverse event (AE) was thrombocytopenia (27%), infections (20%), anemia (14%), and febrile neutropenia (11%). AEs of special interest included tumor flare in 4 patients and myelodysplastic syndrome and lung malignancy in 1 patient each.

Seventy-seven percent of patients had AEs leading to dose interruption, 34% required dose reduction, and 30% discontinued because of AEs.

In June 2019, the FDA approved polatuzumab vedotin in combination with bendamustine and rituximab (Rituxan) for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma who had received ≥2 prior therapies.

Diefenbach C, Kahl BS, Banerjee L, et al. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed/refractory follicular lymphoma: primary analysis of the full efficacy population in a phase Ib/II trial. Presented at 2019 ASH Annual Meeting; December 7-10, 2019; Orlando, FL. Abstract #126. bit.ly/36c38zb.

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