BackgroundOver the last 15 years, improvements in patient management and treatments have been associated with longer survival in patients with multiple myeloma (MM). The Connect MM Registry is a long-running, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM (NDMM). We assessed the demographics, clinical characteristics, and treatment patterns of long-term survivors (LTS) enrolled in this registry. MethodsAdults with NDMM (N=3,011) were enrolled from 250 community, academic, and government sites across the US from 2009-2016. Baseline characteristics, treatment patterns, quality of life (QoL), and overall survival (OS) were examined among LTS, defined as patients with follow-up of ≥8 years after enrollment. ResultsAs of February 7, 2023, 518 patients were LTS and 2,493 were non-LTS. LTS were generally younger and had better performance status at enrollment compared with non-LTS. Most (65%) LTS received stem cell transplants and few (2%) experienced disease progression within 6 months of starting first line of therapy. At data cutoff, 63% of LTS were still on treatment at their most recent visit. QoL scores and QoL questionnaire completion rates were consistently higher among LTS than non-LTS. The estimated 8-year OS rate of all patients enrolled in the registry was 40%, comparable to an observed 8-year survival of 39% from the Surveillance, Epidemiology, and End Results (SEER) database. ConclusionThis analysis provides insights on long-surviving patients with MM using real-world data and therefore presents generalizability beyond data obtained in long-term follow-up of clinical trials, underscoring the need for longitudinal follow-up through registries. DisclosuresHoward R. Terebelo, James Omel, Lynne I. Wagner, James W. Hardin Brian G. Durie, Mohit Narang, Kathleen Toomey, and Rafat Abonour report serving on a scientific steering committee for Bristol Myers Squibb. Robert M. Rifkin reports serving on a scientific steering committee for Bristol Myers Squibb; employment, stock, and other ownership interests with McKesson; participation on data safety monitoring board for CARsgen; and advisory role with Amgen, Bristol Myers Squibb; Coherus BioSciences, Genmab, Fresenius Kabi, and Janssen. Sikander Ailawadhi reports serving on a scientific steering committee for Bristol Myers Squibb; consulting fees from BeiGene, Bristol Myers Squibb, Cellectar, GSK, Janssen, Pfizer, Regeneron, Sanofi, and Takeda; and research funding from AbbVie, Amgen, Ascentage, Bristol Myers Squibb, Cellectar, GSK, Janssen, Pharmacyclics, and Sanofi. Cristina J. Gasparetto reports serving on a scientific steering committee for Bristol Myers Squibb; support for travel from Bristol Myers Squibb, Karyopharm, and Sanofi; advisory role for Bristol Myers Squibb, Janssen, and Pfizer; and for Bristol Myers Squibb, Karyopharm, and Sanofi. Prashant Joshi, E. Dawn Flick, Edward Yu, and Ying-Ming Jou report employment and stock and other ownership interests with Bristol Myers Squibb. Hans C. Lee reports serving on a scientific steering committee for Bristol Myers Squibb; consulting fees from Allogene, Bristol Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Monte Rosa Therapeutics, Pfizer, Regeneron, Sanofi, and Takeda; and grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Regeneron, and Takeda. Sundar Jagannath reports serving on a scientific steering committee for Bristol Myers Squibb; consulting fees from Bristol Myers Squibb, Janssen, Karyopharm Therapeutics, Legend Biotech, Regeneron Sanofi, and Takeda; support for travel from ASCO, ASH, and IMS; participation on data safety monitoring boards for Bristol Myers Squibb, Janssen, and Sanofi; and leadership or fiduciary role for ASH, IMS, and SOHO. MicroAbstractPatient characteristics, treatment patterns, quality of life, and survival were analyzed among long-surviving patients of multiple myeloma from the Connect® MM Registry. Long survivors were generally younger and healthier at diagnosis when compared with non-long survivors. The results provided insights beyond the long-term follow-up of clinical trials, indicating the importance of real-world longitudinal follow-up.

IntroductionThe discontinuation of third-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is not well understood. We aim to evaluate treatment-free remission in patients with CML-CP who discontinue ponatinib. MethodsWe retrospectively reviewed 361 patients who attempted TKI discontinuation between November 2005 and February 2024 and identified those receiving ponatinib at the time of discontinuation. Molecular relapse-free survival (MRFS) was calculated from the time of ponatinib discontinuation to the date of loss of major molecular response (MMR) or last follow-up. ResultsEleven patients discontinued ponatinib. Before ponatinib discontinuation, patients were on TKI therapy for a median of 146.6 months and on ponatinib for a median of 67.5 months. The median number of TKIs prior to starting ponatinib was 2 (range, 1-3). The median durations of sustained MR4 and MR4.5 before ponatinib discontinuation were 32.8 and 29.4 months, respectively. After a median follow-up of 60.3 months, the 60-month MRFS rate was 53%. Five patients lost MMR; their median MR4.5 duration was 5 months before ponatinib discontinuation. ConclusionPonatinib discontinuation is feasible in patients with CML-CP failing prior TKIs. Patients who achieve sustained MR4.5 for at least 2 years have the highest likelihood of remaining in treatment-free remission following ponatinib discontinuation. Micro-abstractWe aim to evaluate treatment-free remission in patients with chronic myeloid leukemia in chronic phase (CML-CP) who discontinue ponatinib. We identified 11 patients who failed prior tyrosine kinase inhibitors (TKIs) and were receiving ponatinib at the time of discontinuation. The median durations of sustained MR4 and MR4.5 before ponatinib discontinuation were 32.8 and 29.4 months, respectively. Five patients lost MMR; their median MR4.5 duration was 5 months before ponatinib discontinuation. In summary, ponatinib discontinuation is feasible in patients with CML-CP failing prior TKIs. Patients who achieve sustained MR4.5 for at least 2 years have the highest likelihood of remaining in treatment-free remission following ponatinib discontinuation.

BackgroundMonoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells. MethodWe present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay. Both patients received plasma cell directed therapy. ResultThe first patient received plasma cell directed therapy for a time-limited period and achieved a sustained clinical remission without detectable anti-insulin antibodies. The second patient receives continuous plasma cell directed therapy and is in clinical remission with low values of detectable anti-insulin antibodies. ConclusionPlasma cell directed therapy was effective and safe in our 2 cases of monoclonal IAS. We recommend considering plasma cell directed therapy for these patients.

BackgroundThis noninterventional postauthorization safety study assessed the safety and effectiveness of lenalidomide in patients with transfusion-dependent, International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) associated with isolated deletion of 5q (del[5q]) who were treated in routine care. Patients and MethodsEligible adult patients in the lenalidomide cohort had transfusion-dependent, IPSS Low- or Int-1-risk MDS and isolated del(5q) and had received ≥ 1 dose of lenalidomide between 2014 and 2022. The primary endpoint was the 24-month cumulative incidence of acute myeloid leukemia (AML) progression. Overall survival (OS) was estimated by Kaplan–Meier analysis and safety data were collected. ResultsIn total, 296 patients received ≥ 1 dose of lenalidomide (lenalidomide cohort, safety population) and 277 had received ≥ 1 complete cycle of lenalidomide (primary population). In the safety population, 44.3% of patients completed 3-year follow-up and 55.1% discontinued, with 33.1% discontinuing due to death. In the primary population, 24-month cumulative incidence of AML progression was 12.7% (95% confidence interval, 8.9%-17.1%) and estimated OS probability was 78.3% at 24 months and 63.9% at 36 months. Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There were no new safety signals. ConclusionThese real-world data support the established benefit-risk profile of lenalidomide in transfusion-dependent IPSS Low- or Int-1-risk MDS with isolated del(5q).

BackgroundDisparities in access to triplet and quadruplet therapy for multiple myeloma (MM) patients remain a challenge in the United States. We aimed to investigate demographic and socioeconomic factors influencing treatment access using NCDB data. Patients and MethodsWe analyzed 101,867 MM patients diagnosed between 2004 and 2020. Multinomial logistic regression and multivariable cox regression were employed to assess factors influencing treatment access and survival, respectively. ResultsBlack patients exhibited significantly lower odds of receiving triplet and quadruplet therapy compared to White patients. Socioeconomic factors such as insurance status and household income also influenced treatment access. However, Black and Hispanic patients demonstrated better survival outcomes despite disparities in access. ConclusionRacial, socioeconomic, and insurance-related disparities persist in access to optimal MM therapy in the USA. Addressing these barriers is essential for ensuring equitable healthcare delivery and improving patient outcomes.

IntroductionWe performed a retrospective analysis of patients with multiple myeloma (MM) receiving palliative radiotherapy (RT) and assessed factors associated with local control, with a focus on dose/fractionation and cytogenetics. Materials and MethodsWe included patients who received palliative RT for MM at our institution. Cytogenetics were collected via fluorescence in situ hybridization. Follow-up imaging was used to assess local control. ResultsA total of 239 patients with 362 treated lesions were included. Eighty-six (36.0%) patients had high-risk cytogenetics. Most lesions received 20 Gray (Gy) in 5 fractions (131, 36.2%), 8 Gy in 1 fraction (93, 25.7%), or 30 Gy in 10 fractions (48, 13.3%). At a median follow-up of 4.3 years, 4-year local progression was 13.4% (95% confidence interval [CI]: 10.3-17.5). No cytogenetic abnormalities were correlated with local progression, nor were double- and triple-hit status. There was a nonsignificant trend toward association between number of treated lesions and local progression (HR for >3 vs. 1: 2.43 [95% CI: 0.88-6.74], P = .059). Among patients with >3 treated lesions, equivalent dose in 2 Gy fractions ≥20 Gy reduced progression (HR: 0.05 [95% CI: 0.01-0.23], P = .0001). ConclusionIn this large study of patients with MM, modern palliative RT achieved excellent rates of long-term local control. Although there was no dose-response observed in the overall cohort, patients with high volume symptomatic disease may benefit from EQD2 ≥20 Gy. High-risk cytogenetics did not appear to influence radioresponsiveness, and standard radiation doses appear to be effective for all MM patients regardless of cytogenetics.

PurposeAnemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor–naive and –experienced patients. MethodsAll RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively. ResultsIn the phase 2 study, mean transfusion requirement changed by −1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (−0.1, −0.36, and −0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol. ConclusionThese novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators. Trial registrationClinicalTrials.gov identifiers: NCT02515630, NCT01969838, NCT02101268, NCT04173494.