Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological I
Hematology Disease Topics & Pathways:
Research, clinical trials, Non-Biological therapies, Clinical Research, Combination therapy, Therapies
Methods: Eligible pts ≥18 years with FL Grade I-IIIA or MCL, ≥1 prior therapy, adequate bone marrow and organ function, no prior PI3K or BTK inhibitors, and who signed consent were treated with zandelisib 60 mg on ID (first 7 days of each cycle) and zanubrutinib 80 mg twice daily in 28-day cycles until progression of disease (PD) or intolerance. Imaging was obtained after cycles 2 and 6, and subsequently every 6 months. Response was assessed by investigators using the Lugano criteria. The study has completed enrollment. Herein, we report the FL and MCL cohorts.
Results: 50 pts were treated, 31 with FL (enrolled between Feb 2020 and Oct 2021) and 19 with MCL (enrolled between Jan 2021 and May 2022), with a median age of 67 years (range 40-83). Median number of prior therapies was 2 (range 1-5), 27 pts (54%) had received ≥2 prior therapies, 15 pts (30%) were refractory to last therapy, 14 pts (28%) had a lesion ≥5 cm, and 22 of 31 FL pts (71%) had POD24. As of 23 Jun 2022, the median time on combination therapy is 11.4 months (range 2-29) for FL and 6.5 months (range 1-17) for MCL, with 30 pts (60%) on continued therapy (19 [38%] for ≥12 months). 20 pts (40%) have discontinued therapy (15 [30%] PD; 3 [6%] consent withdrawn; 2 [4%] due to an adverse event (1 neutropenia and 1 DRESS syndrome). In FL the ORR was 80% with a CRR of 20%; in MCL the ORR was 76% with a CR of 35% (Table 1 and Figure 1). In FL with a median follow-up of 11.1 months, the preliminary median progression free survival (PFS) was 22.4 months (95% CI 11.47, NA); in MCL with a median follow-up of 10.8 months, the preliminary median PFS was 10.4 months (95% CI 3.32, NA). Additional follow up is necessary to allow estimates of CRR and duration of responses (DOR). Non-laboratory AEs of any grade (Gr), with Gr 3-4 in parentheses, reported in ≥15% of pts are diarrhea in 32% (2%) of pts, contusion in 20% (0%), headache in 18% (2%), arthralgia in 16% (2%), nausea in 16% (2%) and maculopapular rash in 16% (4%). AEs of special interest include atrial fibrillation, pneumonia, and febrile neutropenia (2 pts [4%] each; all Gr 3), Gr 3 sepsis and Gr 4 DRESS syndrome (1 pt [2%] each). Gr 3-4 laboratory abnormalities include neutropenia in 15 pts (30%), ALT in 6 (12%) and AST in 5 (10%). The only death in the study was a 68-year-old unvaccinated pt with MCL who died of complications of COVID-19.
Conclusions: Zandelisib plus zanubrutinib was well tolerated with no increase in the rate or severity of class-related AEs compared to either agent alone. Few pts (4%) have discontinued due to an AE. We observed high response rates in R/R FL (80%) and MCL (76%). Additionally, responses appear to deepen over time and further follow-up will fully assess the CRR, DOR, and PFS. These results support further evaluation of the combination in B-cell malignancies.
Disclosures: Soumerai: TG Therapeutics: Consultancy, Research Funding; Biogen: Consultancy; Boston Gene: Research Funding; Beigene: Consultancy, Research Funding; GlaxoSmithKline: Research Funding; AstraZeneca: Consultancy; Verastem: Consultancy; Bristol Myers Squibb: Consultancy; MEI: Research Funding; Roche: Consultancy; Moderna: Research Funding; Genentech/Roche: Consultancy, Research Funding; Abbvie: Consultancy; Adaptive Biotechnologies: Research Funding. Diefenbach: FATE Therapeutics: Research Funding; Genentech/Roche: Consultancy, Research Funding; Genmab: Consultancy; Gilead: Current equity holder in publicly-traded company; IMAB: Consultancy; Incyte: Research Funding; Kite: Consultancy; MEI Pharma: Research Funding; Merck: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding; Seattle Genetics: Research Funding. Samaniego: TG Therapeutics: Honoraria. Asch: Gilead Sciences: Research Funding. Jagadeesh: MEI Pharma: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding; Debio pharma: Research Funding; LOXO Pharmaceuticals: Research Funding; Seagen: Research Funding; ATARA Biotherapeutics: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium Pharmaceuticals: Research Funding; AstraZeneca: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees. Lossos: NCI: Research Funding; LRF: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria. Awan: Pharmacyclics: Consultancy, Research Funding; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy; Verastem: Consultancy; Incyte: Consultancy; BeiGene: Consultancy; Johnson and Johnson: Consultancy; Dava Oncology: Consultancy; BMS: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; ADCT Therapeutics: Consultancy; Epizyme: Consultancy; Caribou Biosciences: Consultancy; Cellecter Bisosciences: Consultancy; Janssen: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy; Genentech: Consultancy. Miao: MEI Pharma: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Ghalie: MEI Pharma: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Zelenetz: Abbvie: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; MEI Pharma: Consultancy, Research Funding; Novartis: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria, Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria; BMS/Celgene/JUNO: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.
OffLabel Disclosure: Zandelisib is an investigational agent
See more of: Oral and Poster Abstracts