Catamero, Donna

Multi-agent regimens incorporating immunomodulatory (IMiD®) agents such as thalidomide, lenalidomide, and pomalidomide have become the preferred standard of care for the treatment of patients with multiple myeloma (MM), resulting in improved survival outcomes. Currently, there are three IMiD agents approved for the treatment of MM: thalidomide, lenalidomide, and pomalidomide. Lenalidomide is commonly used to treat patients with newly diagnosed MM and as maintenance therapy following stem cell transplant or after disease relapse. Pomalidomide, the focus of this review, is approved in patients with relapsed/refractory MM (RRMM). Despite survival benefits, IMiD agents each have different safety profiles requiring consideration both prior to starting therapy and during treatment. Adverse event (AE) management is essential, not only to ensure treatment adherence and thus ensure optimal efficacy but also to maintain patient quality of life. Here, we discuss AEs associated with pomalidomide and present five clinically relevant hypothetical case studies in patients with RRMM to provide scenario-driven guidance regarding treatment selection and AE prevention and management in the clinical setting. Lastly, as new treatment approaches continue to be explored in MM, we also discuss novel cereblon E3 ligase modulator (CELMoD™) agents including iberdomide (CC-220) and mezigdomide (CC-92480).

8032 Background: The impact of t(11;14) (16%–24% of MM pts) on prognosis is not fully understood. Consensus is lacking on the effects of induction treatment (tx) on outcomes with t(11;14). The Connect MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with NDMM designed to examine real-world diagnostic patterns, treatment (tx) patterns, clinical outcomes, and HRQoL pt-reported outcomes in pts with NDMM. The impact of t(11;14) on tx outcomes are reported. Methods: Analysis included data from pts from 250 community, academic, and government sites in cohort (C) 1 (9/2009–12/2011) and C2 (12/2012–4/2016), who completed first-line (1L; induction) tx and were tested for t(11;14) by FISH or cytogenetics. Primary end points (progression-free survival [PFS] and overall survival [OS]) were measured from start of 1L tx to earliest event (PFS, death or progression; OS, death), loss to follow-up, or data cutoff, adjusted for baseline (BL) risk factors. A sensitivity analysis excluding pts with concomitant cytogenetic abnormalities [del 17p, t(4;14), t(14;16), 1q+] was also performed. Results: By 1/2018, 3011 pts were enrolled; 2938 were treated. Of 1574 enrolled pts tested for t(11;14), 378 were t(11;14)+ and 1196 were t(11;14)−. More pts in C2 vs C1 were t(11;14)+ (60% vs 40%). BL characteristics were similar between groups. t(11;14) status did not affect PFS ( P= NS) or OS ( P= NS; Table). Pts in C1 and C2 received similar 1L txs (IMiD agent + proteasome inhibitor [PI], 30% vs 42%; PI only, 42% vs 43%; IMiD agent only, 17% vs 11%). Results were similar when pts with concomitant abnormalities were excluded. Conclusions: Results of this analysis suggest that t(11;14) does not affect PFS and OS outcomes in NDMM pts. Clinical trial information: NCT01081028. [Table: see text]

Background: MM clinical trials often have stringent eligibility criteria that limit the enrollment of patients (pts) reflective of the general patient population (Shah, Clin Lymphoma Myeloma Leuk 2017). The Connect® MM Registry, a prospective observational study of pts with newly diagnosed MM (NDMM) in the US, provided the opportunity to examine differences between pts with MM who were identified as RCT-eligible vs -ineligible, to observe the generalizability of clinical trial results to real-world clinical settings. Differences in baseline characteristics, treatment, clinical outcomes, and HRQoL were examined in RCT-eligible and -ineligible pts from this registry, which represents an unselected, broad real-world population. Methods: Pts with NDMM were enrolled at 250 community, academic, and government sites. Eligible pts were ≥18 y of age with symptomatic MM diagnosed ≤2 months preenrollment per the International Myeloma Working Group (IMWG) criteria. For this analysis, pts were considered ineligible for RCT per the following key exclusion criteria previously described: absolute neutrophil count ≤1.5 × 109/L, platelet count ≤75 × 109/L, creatinine >2.5 mg/dL, AST/ALT >3 times the ULN, peripheral neuropathy grade >2; ECOG PS 3/4; history of myelodysplastic syndromes/other hematologic malignancies, or solid tumors (Shah 2017). Sites administered pt HRQoL questionnaires and provided clinical data at baseline and quarterly during follow-up until death or study discontinuation. Differences in HRQoL at baseline, changes from baseline to 1 and 2 years, and survival outcomes, adjusted for covariates via propensity score, were compared between RCT-eligible/-ineligible pts. Results: Of the 3011 pts enrolled, 2873 pts met the CRAB (hyperCalcemia, Renal failure, Anemia, and Bone disease) criteria per IMWG at enrollment. Of these, 1622 (56.5%) were identified as RCT-eligible and 1251 (43.5%) as RCT-ineligible (data cut-off February 7, 2019). Both groups were similar in median age, sex, race, and ethnicity distribution, although the RCT-ineligible group had more pts aged ≥75 y (26.3% vs 23.2%) and more pts with ECOG PS 3/4 (6.2% vs none). Overall, 34.5% of RCT-ineligible pts received a transplant vs 42.8% of RCT-eligible pts. More RCT-ineligible pts had ISS stage III disease (39.4% vs 19.8%), elevated calcium (≥11.5 mg/dL; 12.7% vs 6.8%), elevated creatinine (>2.0 mg/dL; 40.3% vs 6.5%), and low hemoglobin (<10 g/dL or >2 g/dL <LLN; 60.8% vs 40.3%). Use of triplet treatment (54.2% vs 56.2%) and alkylator (24.9% vs 20.1%) was similar between the RCT-ineligible/-eligible groups. Lenalidomide + bortezomib + dexamethasone (RVd) was the most common initial therapy, and R was the most common maintenance therapy in both groups, but fewer RCT-ineligible pts received RVd as initial therapy (23.9% vs 31.0%) and R as first maintenance regimen (18.1% vs 22.7%). Absolute baseline HRQoL scores were significantly higher, indicating better HRQoL, in RCT-eligible (115.9) vs -ineligible (111.5) pts on the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM) Total score (P=0.007), FACT-MM Trial Outcome Index (74.3 vs 70.3, P=0.002), and FACT-MM Subscale (37.3 vs 35.5, P=0.003). Scores were similar for EuroQol-5D Overall Index (0.73 vs 0.72, P=0.5) and Brief Pain Inventory (3.42 vs 3.43, P=0.9). Both RCT-eligible and -ineligible pts showed significant improvement in HRQoL from baseline at years 1 and 2, although the magnitude of improvement was similar between both groups (Fig. 1a and b). RCT-ineligible pts showed significantly shorter median PFS and OS vs RCT-eligible pts (Fig. 2 & 3, respectively). Conclusions: The CONNECT MM registry provided the opportunity to examine key differences between RCT-eligible and -ineligible pts. By applying common RCT eligibility criteria, a substantial proportion of MM pts (43.5%) in this real-world population may have been ineligible to participate in a RCT. RCT-ineligible pts had advanced disease, poor performance status, and poor laboratory parameters at baseline vs RCT-eligible pts, which could affect PFS and OS. These findings enhance our understanding of HRQoL among MM pts, which at present, is largely based on RCT participants. A similar magnitude of HRQoL improvement in both groups at 1 and 2 years suggests the need to evaluate RCT eligibility criteria in MM to help broaden enrollment and maximize external validity. Disclosures Wagner: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Toomey:Celgene: Consultancy. Ailawadhi:Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding. Jagannath:Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; AbbVie: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Rifkin:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Lee:Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline plc: Research Funding; Amgen: Consultancy, Research Funding. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Catamero:Celgene: Employment, Equity Ownership. Abonour:BMS: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.