Light Chain Multiple Myeloma - Clinical Characteristics and Outcomes

Introduction: Light chain multiple myeloma (LCMM) is a distinct subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains, unlike the common form of MM that produces the complete immunoglobulin. There is a paucity of literature on the specific tumor cell alterations leading to light chain-only disease as opposed to the typical presentation in MM. Additionally, data on treatment response and outcomes in this subgroup of patients is sparse. This study explores the differences in baseline characteristics, including cytogenetic abnormalities and treatment response between LCMM and multiple myeloma with heavy chain involvement.

Materials and Methods: We reviewed patient charts to obtain clinical and laboratory information for individuals diagnosed with LCMM and those with heavy chain MM (comparison cohort) from 2004 to 2022. Patients were matched for age, sex, and year of diagnosis. Data collected included treatment assessment, overall survival, and progression-free survival (PFS). Associations between outcomes and categorical variables were analyzed using the chi-square test, while the Mann-Whitney U test was employed to compare medians. Progression-free survival following initiation of initial therapy and overall survival were assessed using Kaplan-Meier analysis. The Mayo Clinic Institutional Review Board (IRB) approved the study.

Results: We identified 848 patients, representing 17.1% of newly diagnosed MM cases. The median age of the LCMM cohort was 63 years (range 16-92), with a female-to-male ratio of 1:5. The LCMM cohort had higher levels of lactate dehydrogenase (LDH), beta-2 microglobulin (p<0.0001), higher baseline creatinine (p<0.0001) and calcium (p<0.0001). The two cohorts had no significant difference in the International Staging System (ISS) or revised ISS (R2-ISS). Additionally, hemoglobin (Hb) and white blood cell count at presentation were higher in the LCMM cohort.

Chromosome 1 abnormalities were lower in the LCMM cohort: 1q gain (OR-0.7; 95% CI: 0.6-0.9) and 1p deletion (OR-0.7; 95% CI: 0.6-0.9, p=0.02). Likewise, the frequencies of trisomies and hyperdiploidy were lower in the LCMM cohort, with odds ratios of 0.32 (p=0.012) and 0.37 (p<0.001), respectively. The frequencies of translocations t(4;14) (OR-0.35, p<0.001) and t(14;16) (OR-0.6, p=0.03) were lower in LCMM compared to heavy chain MM. In contrast, the frequencies of t(11;14) (OR-3.4) and t(6;14) (OR-4.9) and deletion of 13q(OR-1.3) was higher in the LCMM cohort. There was no significant difference in the occurrence of del(17p)/TP53 abnormalities.

The median PFS after the first regimen was shorter in the LCMM cohort (23 months vs. 27 months, p=0.03), and this difference remained significant after adjusting for baseline adverse prognostic indices and treatment regimen. Median PFS in LCMM patients with monoclonal antibody (Mab) as part of their treatment was 37 months vs. 23 months (Proteasome Inhibitor or immunomodulator-based regimen without Mab), though this difference is not statistically significant p=0.87. No significant difference was found in overall survival between the two groups.

Conclusion: This study highlights unique features of light chain multiple myeloma, including increased frequencies of specific cytogenetic abnormalities. Further evaluation of observed differences in cytogenetic abnormalities may enhance our understanding of LCMM and potentially guide baseline treatment choices to improve outcome.

Gertz:Ionis/Akcea: Honoraria; Alnylym: Honoraria; Prothena: Other: personal fees; Abbvie: Other: personal fees for Data Safety Monitoring board ; Johnson & Johnson: Other: personal fees; Medscape: Honoraria; Sanofi: Other: personal fees; Alexion: Honoraria; Dava Oncology: Honoraria; Astra Zeneca: Honoraria; Janssen: Other: personal fees. Dispenzieri:HaemaloiX: Research Funding; Alnylam: Research Funding; Janssen: Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Research Funding; Alexion: Consultancy, Research Funding. Muchtar:Protego: Consultancy. Kapoor:Kite: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Karyopharm: Research Funding; Loxo Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ichnos: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Keosys: Consultancy. Kourelis:Novartis: Research Funding; Pfizer: Research Funding. Dingli:Genentech: Consultancy; Sorrento: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; K36 Therapeutics: Research Funding; MSD: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Leung:AbbVie: Current holder of stock options in a privately-held company; Checkpoint Therapeutics: Current holder of stock options in a privately-held company. Cook:Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Lin:Regeneron: Consultancy; Sanofi: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Legend: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy. Hwa:MultiMedia Medical, LLC: Consultancy; Pfizer: Other: Consulting fee located to Mayo Research fund; GSK: Honoraria; Shield Therapeutics: Honoraria; Janssen: Honoraria. Kumar:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Roche: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding.