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Obinutuzumab Plus Idelalisib Effective Combo Regimen for WM

Phase 2 study findings suggest obinutuzumab in combination with idelalisib is an effective treatment option for patients with relapsed/refractory Waldenström macroglobulinemia ([WM] Blood Adv. 2021;5(9):2438-2446.)

According to Cécile Tomowiak, MD, Hematology Department and Centre d’Investigations Cliniques, University Hospital, Poitiers, France, and colleagues, the aim of the study was to determine the safety and efficacy of a fixed-duration chemotherapy-free treatment compared to usual therapy.

Across 21 sites between March 2017 and July 2018, a total of 50 patients with R/R MM who had between 1 to 3 prior treatment regimens were enrolled in the study. During the induction phase, 48 patients received obinutuzumab and idelalisib for 6 cycles. After that, 27 patients moved forward to the maintenance phase of idelalisib alone for ≤2 years.

The primary end point of the study was PFS, calculated from the date of inclusion to progression or death. Secondary end points included overall response rate (ORR), response rates at months 8 and 24, overall survival (OS), time to at least a minor response (MR), time to treatment failure (TTF), and time to new treatment.

The best responses after a median of 6.5 months included very good partial responses in 5 patients, partial response in 27 patients, and MR in 3 patients, leading to an overall response rate (ORR) of 71.4% (95% CI, 56.7-83.4) and a major response rate (MRR) of 65.3% (95% CI, 50.4-78.3). Stable disease and progressive disease were seen in 5 and 3 patients, respectively.

After a median follow-up of 25.9 months, the median PFS was 25.4 months (95% CI, 15.7-29) and the PFS rates at 12 and 24 months were 75.5% (95% CI, 64.4-88.6) and 55% (95% CI, 42.7-70.9), respectively. The median TTF was 25.6 months (95% CI, 19.9-30.4). OS rates at 12 months were 97.8% (95% CI, 94.1-100) and at 24 months were 89.8% (95% CI, 81.7-98.7). In all, 28 patients progressed.

Univariate analysis focusing on molecular screening found no major impact of CXCR4 genotypes on responses and survival, but, there was a negative impact of TP53 mutations on survival.

Twenty-six patients were removed from the study over side effects. The most common included neutropenia (9.4%), diarrhea (8.6%), and liver toxicity (9.3%).

“The combination of idelalisib + obinutuzumab is effective in R/R WM. Nonetheless, the apparent lack of impact of genotype on outcome could give new meaning to targeting of the phosphatidylinositol 3-kinase pathway in WM,” Dr Tomowiak and colleagues said.—Emily Bader

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