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3315 Impact of Multiple High-Risk Cytogenetic Abnormalities on the Survival Outcomes of Patients with Primary Plasma Cell Leukemia

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Adult, Translational Research, Clinical Research, Health outcomes research, Genomics, Biological Processes, Technology and Procedures, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Adrian A Almodovar Diaz1, Samhar Alouch2*, Angela Dispenzieri, MD3, Udit Yadav, MBBS4*, Francis Buadi, MD3, David Dingli, MD, PhD3, Eli Muchtar, MD3, Nelson Leung, MD5, Taxiarchis Kourelis, MD3, Rahma M Warsame, MD3, Ronald S Go, M.D.6, Moritz Binder, MD3, Joselle Cook, MBBS3, Miriam Hobbs, APRN, CNP, DNP3*, Yi Lisa Hwa, APRN, DNP, CNP3, Amie Fonder, PA-C, MS7*, Michelle G. Rogers, CNP3*, Suzanne R Hayman, MD3, Yi Lin, MD, PhD3, Mustaqeem A. Siddiqui, MD, MBA3, Robert A. Kyle, MD3, Morie A. Gertz, MD3, Vincent Rajkumar, MD3* and Wilson I. Gonsalves, MD8

1University of Puerto Rico School of Medical Sciences, San Juan, PR
2Alfaisal University, Riyadh, Saudi Arabia
3Division of Hematology, Mayo Clinic, Rochester, MN
4Division of Hematology/Oncology, Mayo Clinic Arizona, Phoenix, AZ
5Division of Nephrology, Hematology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
6Division of Medical Oncology, Mayo Clinic, Onalaska, WI
7Hematology, Mayo Clinic, Rochester, MN
8Division of Hematology, Mayo School of Graduate Medical Education, Rochester, MN

INTRODUCTION

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) with poor survival outcomes. Fluorescence in situ hybridization (FISH) evaluation is essential for the initial risk stratification in MM, and the presence of multiple high-risk (HR) cytogenetic abnormalities by FISH portends a worse prognosis in MM. We have previously observed that the presence of HR cytogenetic abnormalities by FISH at diagnosis is known to confer a poor overall survival (OS) in patients with pPCL. However, less is known about the cumulative effect of multiple HR cytogenetics abnormalities compared to a single HR cytogenetic abnormality on the OS outcomes of patients with pPCL.

AIM

To evaluate the prognostic implications of additive HR cytogenetics abnormalities by FISH in patients with pPCL treated with novel agents.

METHODS

We evaluated patients with newly diagnosed pPCL at the Mayo Clinic Comprehensive Cancer Center from 2014 – 2023 that received induction with novel agent combinations. pPCL was defined as patients meeting the diagnostic criteria for MM with 5% or more circulating plasma cells (cPCs) present on morphologic evaluation of their peripheral blood smear. HR cytogenetics abnormalities by FISH was defined by the presence of any one of the following: 1q gain/amplification, t(4;14), t(14;16), t(14;20), and del(17p). Time to next treatment (TTNT) and OS analysis were performed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Statistical analyses were performed using the SAS biostatistical software JMP 17.0.1 (SAS Institute Inc).

RESULTS

We included 89 patients with newly diagnosed pPCL who received novel agents as first-line therapy between 2014 to 2023. The median follow-up was 45 months (95% CI: 35 – 65). At diagnosis, the median bone marrow plasma cell content was 80% (Range: 10 – 100), and the median cPC% on the peripheral smear was 21% (range: 5 - 85). There were 51 patients (59%) who had 20% or more cPCs on their peripheral smear. There was a preponderance of pPCL patients who had t(11; 14) as their primary cytogenetic abnormality (43%). The median lines of therapy received were 2 (Range: 1 – 9). There were 12 (13%) patients who received intensive induction therapy containing continuous infusional chemotherapy regimens at the onset of their diagnosis. Of the remaining patients, 35 (45%) were treated with a quadruplet (anti-CD38 antibody, proteasome inhibitor and immunomodulator), 24 (31%) with a triplet (proteasome inhibitor and immunomodulator) and 18 (23%) with a doublet (proteasome inhibitor only). The median OS for all pPCL patients in this cohort was 47 months (95% CI: 37 – 100). However, when stratified by cytogenetic risk, the median OS was 101 months (95% CI: 57 – NR) for those patients without any HR cytogenetic abnormalities (N = 24, 27%) vs. 37 months (95% CI: 22 – 63) for those with one or more HR cytogenetic abnormalities (N = 65, 73%) (P = 0.006). Of the patients with any HR cytogenetic abnormalities, 33 (36%) had one HR cytogenetic abnormalities and 32 (34%) had two or more HR cytogenetic abnormalities. The median OS for patients with one compared to two or more HR cytogenetic abnormalities were 47 (95% CI: 38 – 111), and 22 (95% CI: 17 – 37) months, respectively (P = 0.031). The median TTNT was 22 months (95% CI: 16 – 58) for those patients without any HR cytogenetic abnormalities vs. 16 months (95% CI: 9 – 21) for those with one or more HR cytogenetic abnormalities (P = 0.09). The median TTNT from the time of diagnosis for pPCL patients with one compared to two or more HR cytogenetic abnormalities were 18 (95% CI: 6 – 41) and 16 (95% CI: 10 – 19) months, respectively (p = 0.247).

CONCLUSION

Patients with pPCL with more than one HR cytogenetic abnormality had an inferior OS compared to those with only one HR cytogenetic abnormality, implicating the additive adverse effects of multiple HR cytogenetics abnormalities. In contrast, patients with pPCL without any HR cytogenetic abnormalities had a relatively long median OS (over 100 months).

Disclosures: Dispenzieri: HaemaloiX: Research Funding; BMS: Consultancy, Research Funding; Janssen: Research Funding; Alexion: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Research Funding; Alnylam: Research Funding. Dingli: Apellis: Consultancy, Honoraria, Research Funding; Genentech: Consultancy; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; MSD: Consultancy, Honoraria; K36 Therapeutics: Research Funding; Regeneron: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sorrento: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Muchtar: Protego: Consultancy. Leung: AbbVie: Current holder of stock options in a privately-held company; Checkpoint Therapeutics: Current holder of stock options in a privately-held company. Kourelis: Novartis: Research Funding; Pfizer: Research Funding. Cook: Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Hwa: MultiMedia Medical, LLC: Consultancy; Pfizer: Other: Consulting fee located to Mayo Research fund; GSK: Honoraria; Janssen: Honoraria; Shield Therapeutics: Honoraria. Lin: Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Legend: Consultancy; Regeneron: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy. Gertz: Johnson & Johnson: Other: personal fees; Astra Zeneca: Honoraria; Janssen: Other: personal fees; Medscape: Honoraria; Prothena: Other: personal fees; Sanofi: Other: personal fees; Alnylym: Honoraria; Ionis/Akcea: Honoraria; Alexion: Honoraria; Abbvie: Other: personal fees for Data Safety Monitoring board ; Dava Oncology: Honoraria.

*signifies non-member of ASH