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S1608: RANDOMIZED PHASE II TRIAL COMPARING LENALIDOMIDE/OBINUTUZUMAB AND UMBRALISIB/OBINUTUZUMAB WITH CHEMOIMMUNOTHERAPY IN EARLY PROGRESSING FOLLICULAR LYMPHOMA (POD24)
Abstract   Peer reviewed

S1608: RANDOMIZED PHASE II TRIAL COMPARING LENALIDOMIDE/OBINUTUZUMAB AND UMBRALISIB/OBINUTUZUMAB WITH CHEMOIMMUNOTHERAPY IN EARLY PROGRESSING FOLLICULAR LYMPHOMA (POD24)

P. M. Barr, H. Li, H. Schoder, A. F. Herrera, W. R. Burack, B. K. Link, C. R. Flowers, O. Weigert, C. Casulo, T. Siddiqi, …
Hematological oncology, Vol.43(S3), p.e233_70094
06/2025
DOI: 10.1002/hon.70094_233

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Abstract

Introduction: Patients (pts) with follicular lymphoma (FL) who relapse within 2 years of initial chemoimmunotherapy (POD24) demonstrate inferior overall survival (Casulo et al. Blood, 2022). S1608 is the first prospective trial focused on this early progressing population. Two targeted regimens, umbralisib/obinutuzumab (U+O) and lenalidomide/obinutuzumab (L+O) were compared with chemotherapy/obinutuzumab (chemo+O). Methods: Eligible pts had centrally reviewed biopsy confirmed FL without transformation, grade 1–3a progressing within 2 years of first line bendamustine or CHOP + anti-CD20 therapy +/− maintenance. Pts were randomized 1:1:1 to 12 cycles of U+O, L+O or 6 cycles of CHOP or bendamustine (the opposite of first line therapy) +O, followed by 6 cycles of O alone. The primary endpoint was the complete remission (CR) rate after 6 cycles using Lugano 2014 criteria. Results: Between 1/2018 and 7/2024, 76 eligible pts were randomized to U+O (n = 24), L+O (n = 27) and chemo+O (n = 25). The median age (range) was 58 (37, 82), 57% were male, 84% were white, 84% had advanced stage disease at diagnosis, 29%/36%/33% were low/intermediate/high-risk by FLIPI, 64%/32% were grade 1/2/grade 3a of FL at registration. 53% and 47% had received first-line CHOP and bendamustine-based therapy respectively and 43% had received rituximab maintenance. The CR rate (95% CI) as per centrally reviewed PET/CT was 64% (43%, 82%) for chemo+O, compared with 52% (31%, 73%) for U+O (p = 0.56) and with 52% (32%, 71%) for L+O (p = 0.41). At a median follow-up of 49 months, the 4-year estimated PFS for the entire cohort was 38% (U+O, 28%; L+O, 49%; chemo+O, 41%) (Figure). Four-year OS for the entire cohort was 69% (U+O, 65%; L+O, 68%; chemo+O, 74%). Median duration of response was 19 months (U+O), not reached (L+O) and 42 months (chemo+O), p = 0.048 comparing L+O and chemo+O. Of the 6 pts who went on to a consolidative autologous stem cell transplant, none have progressed with a median follow-up of 4.9 years (range, 3.5–5 years). Grade (Gr) 5 adverse events (AEs) included respiratory failure due to sepsis/lung infection and COVID, both in pts receiving CHOP+O. Gr 3/4 AEs occurring in > 10% of pts with U+O were neutropenia (17%), leukopenia (13%), COVID / pneumonia (13%) and ALT increase (13%). Gr 3/4 AEs in > 10% with L+O were neutropenia (15%), leukopenia (11%) and anemia (11%). Gr 3/4 AEs in > 10% with chemo+O were neutropenia (32%), leukopenia (32%), thrombocytopenia (12%) and COVID/pneumonia (12%). Conclusions: POD24 FL remains an unmet need as the overall survival for this relatively young prospective cohort is similar to historical outcomes. There was no difference in CR rates or PFS between the targeted regimens and second line chemoimmunotherapy although L+O appeared to demonstrate a longer response duration. Patients who received consolidative high-dose therapy have yet to progress. These results establish a standard for comparison in future trials with this high-risk population.

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