Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Combination therapy, Adult, Clinical Practice (Health Services and Quality), Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Diseases, Indolent lymphoma, Therapy sequence, Real-world evidence, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Methods: We conducted a multicenter retrospective analysis of patients (age ≥18 years) diagnosed with LPL/WM between January 1, 2003, and March 31, 2024 at 7 academic centers in USA. The outcomes of the study included objective response rate (ORR), time to next treatment (TTNT), and overall survival (OS). ORR (CR, VGPR, PR and MR) was calculated according to response criteria per the 6th International Workshop for WM. Associations between baseline characteristics and survival outcomes were evaluated using Cox regression models.
Results: A total of 709 patients were included in this analysis. Patients had a median age of 68 years, with a male predominance (60%), were largely white (91%) and generally had good performance status (53% ECOG 0). An IgM monoclonal gammopathy was present in 98% (n=692) of all patients, followed by IgG in 1% (n=9) and IgA in 0.4% (n=3). An IgM monoclonal protein of ≥3000 mg/dl was present in 33% (n=232) patients and the median M-protein concentration was 1.56 g/dL at diagnosis. Only 6% patients (n=46) required plasmapheresis at some point in their treatment course. MYD88 mutation was present in 85% (448 of 529) patients with available MYD88 results. Mutations in CXCR4 and TP53 were present in 5% (11 of 130) and 14% (41 of 303) of patients respectively at diagnosis.
Twenty percent (n=143) patients were observed with no treatment required. Frontline treatment (1L) with chemo-immunotherapy (CIT) was the most common treatment modality (34%, n=242), with bendamustine-rituximab being the most prescribed CIT (23%, n=160) followed by cyclophosphamide-rituximab combinations (9%, n=60). After CIT, single agent rituximab (R) was used in 22% (154) patients, followed by BTKi with or without anti-CD20 therapies in 11% (81), then proteasome inhibitor (PI) based regimens (8%, 59 patients), and finally chemotherapy without anti-CD20 (C-A) in 3% (19) as 1L. CIT was associated with high ORR (CR+VGPR+PR+MR) at 68%, followed by 54% with BTKi, 53% with PI, and 34% with R monotherapy. The median time to first treatment was similar among these treatment groups (1.5 months, 95% CI 1.3, 1.8, p=0.56).
Second line therapy was initiated in 297 (42%) patients, and 153 (22%) received three or more lines of treatment. The need for second line (2L) treatment was highest for patients initially treated with chemo alone (C-A) at 79% (n=15), followed by R monotherapy at 64% (n=99) and PI-based at 54% (n=46). There was no statistically significant difference in 2L treatment requirement for patients initially treated with CIT or BTKi (hazard ratio 0.04 in both groups). The median time to next treatment (TTNT) between 1L and 2L was longest in the CIT group at 79 months (95% CI: 58, 90) followed by 60 months (95% CI: 23, NR) in the BTKi group, 40 months in the C-A group, and 31 months for R monotherapy.
At median follow-up of 63.9 months, the 7-year and 10-year OS estimates were 81% and 74%, respectively. The choice of 1L treatment did not impact OS in these patients (p=0.74).
Conclusion: This analysis is the largest retrospective, multicenter cohort of patients evaluated in the United States with LPL/WM in the current era of targeted therapies. Our data confirms that LPL generally has a favorable prognosis, with nearly three-quarters of patients surviving 10 years or longer from diagnosis. Approximately one-fifth of patients may not require any treatment, while a similar proportion of higher-risk patients will require three or more lines of therapy. Initial therapy with fixed duration CIT compares favorably with BTKi. Multivariate analysis to study role of patient phenotype and genomics is underway. This study offers a framework for designing future clinical trials, highlighting the need for further research to enhance risk stratification and to provide higher-risk patients with better treatment.
Disclosures: Nakhoda: Beigene: Honoraria; Astra Zeneca: Honoraria; BTG/SERB: Honoraria, Research Funding. Al Hadidi: Sanofi: Consultancy; Pfizer: Consultancy; Janssen: Consultancy. Bair: Kura Oncology: Consultancy. Voorhees: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Research Funding; Incyte/Morphosys: Research Funding; Recordati: Consultancy, Research Funding; Novartis: Consultancy; Viracta: Research Funding. Epperla: Beigene: Speakers Bureau; Lilly: Other: Advisory Board; Novartis: Consultancy; Ispen: Other: Advisory Board; Genetech: Speakers Bureau. Caimi: Genmab: Research Funding; Recordati: Honoraria, Research Funding; Sobi: Honoraria; Abbvie: Honoraria, Research Funding; BMS: Honoraria; Novartis: Honoraria; ADC Therapeutics: Honoraria, Research Funding; Abcon Therapeutics: Current holder of stock options in a privately-held company; Luminary Therapeutics: Membership on an entity's Board of Directors or advisory committees. Grajales-Cruz: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cellectar: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Hernandez-Ilizaliturri: Dava Oncology: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Epizyme: Consultancy; Pharmacyclics: Consultancy; Bristol-Myers Squibb: Consultancy; Ipsen: Honoraria; Morphosys: Consultancy; Gilead: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Honoraria; Kite Pharmaceuticals: Consultancy; BioGene: Consultancy; AbbVie: Consultancy; ADC Therapeutics: Consultancy; AbbVie: Consultancy, Research Funding; Cellectar Biosciences: Consultancy, Research Funding.