Outcomes of Second-Line (2L) Triplet+ Regimens in Patients with Relapsed/Refractory Multiple Myeloma (MM) Following Progression after First-Line (1L) Lenalidomide in the Connect® MM Disease Registry

Introduction: Although survival outcomes are improving for patients (pts) with MM, nearly all pts will have progressive disease (PD) following treatment with 1L regimens. Lenalidomide (R)-based regimens are among the most commonly used 1L treatment regimens in MM, both as initial therapy and as maintenance in both transplant and non-transplant candidates. However, limited evidence exists to guide optimal 2L treatment sequencing following progression on 1L R-based regimens, such as switching immunomodulatory drugs to pomalidomide (P)-based regimens, continuing R-containing regimens, or switching drug class entirely to regimens containing non-immunomodulatory drugs, ie, class switching. This study aimed to describe the effectiveness of 2L treatment among P-containing, R-containing, or non-immunomodulatory drug regimens with ≥3 different agents (triplet+) after progression following a 1L R-containing regimen.

Methods: Data were used from the Connect® MM Disease Registry (NCT01081028), a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM, collected from September 28, 2009 to February 7, 2022. Eligible pts were ≥18 years of age at diagnosis of MM, were relapsed or refractory to a 1L R-containing regimen, and received triplet+ regimens in 2L. Regimens were separated into 3 categories for analysis: P-containing, R-containing, and non-immunomodulatory drug regimens. Date of 2L initiation was defined as index. Patient characteristics, pre- and post-index treatment patterns, and clinical response in 2L were summarized using descriptive statistics. Time to progression, defined as time from index to progression (death is censored), was estimated using the Kaplan-Meier method.

Results: Overall, 279 pts beginning 2L triplet+ regimens were included in this analysis, including 79 pts receiving P-containing regimens, 111 pts receiving R-containing regimens, and 89 pts receiving non-immunomodulatory drug regimens. Demographic and baseline characteristics are shown in Table 1. Median (interquartile range [IQR]) time from 1L treatment initiation to PD was 36.4 (17.7-57.2), 25.1 (13.2-39.7), and 23.0 (9.5-37.2) months (mo) in the P-, R-, and non-immunomodulatory drug-containing cohorts, respectively. Overall, 65.9% of pts were treated with R, bortezomib (V), and dexamethasone (d) (RVd), which was the most common 1L regimen.

Most eligible pts received triplet regimens in 2L, with 10.8% of pts receiving ≥4 drugs in 2L (Table 2). The 3 most common regimens among pts treated with P were carfilzomib (K)/Pd (34.2%), daratumumab (D)/Pd (32.9%), and elotuzumab (E)/Pd (8.9%). RVd (31.5%), KRd (20.7%), and ixazomib (I)/Rd (18.0%) were the 3 most common R-containing regimens in 2L, and cyclophosphamide (C)/Vd (43.8%), DVd (12.4%), and KCd (7.9%) were the most common non-immunomodulatory drug regimens in 2L.

Median follow-up since index ranged from 11.7 mo in the R-containing cohort to 13.1 mo in the P-containing cohort (Table 2). Median duration of 2L treatment was 6.9, 5.7, and 3.8 mo in the P-, R-, and non-immunomodulatory drug-containing cohorts, respectively. Investigator-assessed response of VGPR or better was demonstrated in 38.0%, 23.4%, and 22.5% of pts in the P-, R-, and non-immunomodulatory drug-containing cohorts, respectively, while an overall response was demonstrated in 60.8%, 46.8%, and 49.4% of pts in the P-, R-, and non-immunomodulatory drug-containing cohorts, respectively. Median time to progression was longest in the P-containing cohort at 18.7 mo, and shortest in the R-containing cohort at 15.0 mo. At 78 weeks, 51.5%, 43.9%, and 39.2% of pts remained progression-free in the P-, R-, and non-immunomodulatory drug-containing cohorts, respectively.

Conclusion: Pts on 2L MM treatment post-R received a variety of therapies. This descriptive analysis showed that pts treated with 2L P-containing triplet+ regimens had the highest rate of clinical response and time to progression versus R-containing triplet+ regimens or non-immunomodulatory drug-containing triplet+ regimens. This real-world analysis suggests that 2L P-containing regimens without class-switching to a non-immunomodulatory drug based regimen after progression on 1L R-containing regimens can lead to deep and durable responses. Further evaluations utilizing larger sample sizes, and/or more specific treatment subgroups are needed to confirm these findings.

Lee:Sanofi: Consultancy; GSK: Consultancy, Research Funding; Janssen: Research Funding; Amgen: Research Funding; Regeneron: Research Funding; Oncopetides: Consultancy; Genentech: Consultancy; Monte Rosa Therapeutics: Consultancy; Karyopharm: Consultancy; Immunitas Therapeutics: Consultancy; Legend Biotech: Consultancy; Pfizer: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding. Abonour:Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; GSK: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Prothena: Honoraria. Durie:Celgene/BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Gasparetto:karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Oncopeptides: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hardin:BMS: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Narang:J&J: Honoraria; BMS: Consultancy, Honoraria. Rifkin:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS (celgene): Honoraria, Membership on an entity's Board of Directors or advisory committees; Fresenius/Kabi: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; McKesson: Current Employment, Current equity holder in publicly-traded company; Coherus: Honoraria, Membership on an entity's Board of Directors or advisory committees; GenMab: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Toomey:BMS: Consultancy. Wagner:Celgene/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Slaff:Merck (Spouse): Current Employment; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Danforth:BMS: Current Employment. Anand:Pfizer: Ended employment in the past 24 months; BMS: Current Employment; Amgen: Current equity holder in publicly-traded company. Yu:BMS: Current Employment, Current equity holder in publicly-traded company, Other: travel and accommodation expenses. Tang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jagannath:Legend Biotech: Consultancy; Karyopharm: Consultancy; BMS: Consultancy; Janssen Pharmaceuticals: Consultancy; Sanofi: Consultancy; Takeda: Consultancy.