According to the results of a new study, fixed-duration chemotherapy-free treatment with obinutuzumab and idelalisib is efficacious in symptomatic patients with relapsed/refractory Waldenström macroglobulinemia (R/R WM); however, toxicity appears to be a limitation. The findings were published in Blood Advances.
The phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT02962401) evaluated the safety and efficacy of the combination treatment in patients with R/R WM. For induction therapy, the patients received 6 cycles of continuous oral idelalisib (150 mg, twice daily) with IV obinutuzumab (28-day cycle; 100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15 of cycle 1, then on day 1 of cycles 2-6) followed by maintenance therapy with idelalisib alone for ≤2 years. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR), response rates at months 8 and 24, and overall survival OS.
Among 49 enrolled patients (median age, 68.5 years), 48 received induction therapy; of those, treatment was discontinued by 14 patients, 7 for progressive disease (PD) and 7 for adverse events (AEs). After the month 8 evaluation, another 7 patients discontinued treatment, 1 for PD and 6 for AEs. Maintenance was initiated in 27 patients. At data analysis (May 20, 2020), 9 patients had completed maintenance and 18 patients had discontinued treatment, 5 for PD and 13 for AEs.
Following induction, 43 patients were evaluable at month 8. The ORR and major response rate estimates were 71.4% (95% CI, 56.7-83.4) and 65.3% (95% CI, 50.4-78.3), respectively. The best responses were reached after a median of 6.5 months (interquartile range, 3.4-7.1; range, 2.6-22.1). There were 5 very good partial responses, 27 partial responses, and 3 minor responses. At a median follow up of 25.9 months, the median PFS was 25.4 months (95% CI, 15.7-29.0).
Overall, AEs and PD led to treatment discontinuation in 53% and 26% of patients, respectively. There were 124 grade ≥3 AEs and 56 serious AEs in 43 and 36 patients, respectively. The most frequent AEs (any grade) were neutropenia (19.4%), infection (18.6%), liver toxicity (9.3%), and diarrhea (8.5%). No grade 5 AEs were reported.
The primary limitations of the study included the small sample size, which limited the ability to evaluate subgroups, and the toxicity of the treatment itself.
“[T]here is a need to develop new approaches in patients who are refractory to BTK inhibitors. This population may benefit from this therapeutic option, which could be investigated in further clinical trials,” the authors wrote. “[C]onsidering the potential efficacy of this class of agents, next-generation PI3K inhibitors associated with obinutuzumab could overcome the toxicity profile observed in this phase 2 trial and may be a reasonable treatment option when standard therapies have been exhausted.”
Disclosure: The study author(s) declared the research was supported by Roche and Gilead Sciences. Please see the original reference for a full list of authors’ disclosures.
Tomowiak C, Poulain S, Herbaux C, et al. Obinutuzumab and idelalisib in symptomatic patients with relapsed/refractory Waldenström macroglobulinemia. Blood Adv. 2021;5(9):2438-2446. doi:10.1182/bloodadvances.2020003895