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Background: The introduction of proteasome inhibitors (PIs) and lenalidomide as treatment for newly diagnosed multiple myeloma (MM) has led to an increased population of lenalidomide-refractory patients. Limited data are available characterizing current treatments and outcomes in this difficult-to-treat population., Methods: Individual patient-level data were analyzed from the treatment arms of multiple daratumumab studies, including APOLLO, CASTOR, CANDOR, EQUULEUS, ALCYONE, MAIA, GRIFFIN, POLLUX, and CASSIOPEIA. Included patients were PI exposed and lenalidomide refractory, received 1-3 prior lines of therapy (LOT), and had an Eastern Cooperative Oncology Group performance status < 2. Treatments and outcomes were analyzed by number of prior LOT in the lenalidomide-refractory population. Time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method., Findings: Out of 4764 patients, 915 patients (prior LOT, one [n = 114]; two [n = 462]; three [n = 339]) met inclusion criteria. Median follow-up was 29·7 months (range 28·0-31·7). The overall response rate was 55·4 %. Estimated median TTNT was 9·7 months, median PFS was 10·0 months, and median OS was 27·5 months. Response rates and PFS decreased as number of prior LOT increased. Prognostic factors for response, TTNT, PFS, and OS included International Staging System stage, baseline plasmacytoma status, baseline hemoglobin, anti-CD38-refractory status, and cytogenetic risk status., Interpretation: Lenalidomide-refractory patients treated with 1-3 prior LOT have poor PFS and OS, which generally worsen with each additional LOT, highlighting the need for new and effective treatments for this population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KY reports no financial relationships with a pharmaceutical company. HE reports research funding or honoraria and served as a consultant or advisor to Janssen, Amgen, Sanofi, GSK, and BMS/Celgene. JMS, TR, WD, NL, AS, CL, KQ, AL, RC, PC, SV, and JM are employed by Janssen. KC is employed by Janssen and holds equity in BMS. AK is employed by and holds stock in Janssen. LP, NP, and EF are employed by Legend Biotech USA Inc. BD reports research funding or honoraria from, or provided consultancy for, Sanofi, GlaxoSmithKline, Janssen, Amgen, Natera, BMS, Arcellx, Pfizer, Genentech, and Karyopharm Therapeutics., (Copyright © 2024. Published by Elsevier Ltd.)

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes., Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 6 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing., Findings: Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and -1·5 (95% CI -5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI -1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care., Interpretation: Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease., Funding: Janssen Research & Development, Legend Biotech USA., Competing Interests: Declaration of Interests RM reports a consulting or advisory role or honoraria for Amgen, BMS–Celgene, GSK, Janssen, Menarini-Stemline, Pfizer, Sanofi, and Takeda. HY reports honoraria for Astellas. WA reports honoraria, research funding, or travel expenses from Affimed, BioNTech, GSK, Immatics, and Janssen. MCM reports consulting or advisory roles, honoraria, speaker's bureau, or research funding from BeiGene, CDR life, GSK, Pfizer, Siemens, and Janssen Medicine, and hospitality from Janssen. LS reports consulting or advisory roles for BMS and Johnson & Johnson. II reports a consulting role for AbbVie, ADC Therapeutics, Beam Therapeutics, Genmab, Gilead, and Incyte; and holds equity in Gilead. SJH reports consulting or advisory roles, honoraria, research funding, or speaker's bureau for AbbVie, Amgen, Celgene–BMS, Eusa, F Hoffmann-La Roche–Genentech, GSK, Haemalogix, Janssen, Novartis, and Terumo BCT. UAS reports research funding from BMS, and Janssen and consulting or advisory roles with BMS, Janssen, and Sanofi. JMS has stock and other ownership interests in Johnson & Johnson; and is employed by Janssen. MV is employed by Janssen. NL has stock options in Janssen; and is employed by Janssen. KSG has equity and stock options in Janssen and is employed by Janssen. EGK has equity and stock options in Janssen and is employed by Janssen. AS has equity and stock options in Janssen and is employed by Janssen. CL is employed by Janssen. JG is employed by Janssen. QL is employed by Janssen. WD is employed by Janssen. OCF has equity in Legend and is employed by Legend. EF is employed by Legend. NP has equity in Legend; and is employed by Legend. LK reports a consulting role or honoraria for AbbVie, Amgen, Celgene, GSK, Janssen, Sanofi, and Takeda. KW reports a consulting role, honoraria, or research funding for AbbVie, Amgen, Adaptive Biotech, AstraZeneca, BeiGene, BMS–Celgene, GSK, Janssen, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda. AKM and HM declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Approvals of chimeric antigen receptor T-cell (CAR-T) therapies for relapsed/refractory multiple myeloma (RRMM) represent advancements in treatment options for a hard-to-treat population. Nursing care during CAR-T therapy is crucial for patients, their caregivers, and the broader CAR-T therapy care team. This manuscript provides an overview of the CAR-T therapy administration process and describes practical considerations for nursing professionals working with patients who receive CAR-T therapy., Data Sources: Current literature describing CAR-T therapies for RRMM and published guidelines on nursing care during CAR-T therapy administration were identified from a PubMed database search. Literature was synthesized with practical considerations from nurses and nurse practitioners with expertise in the administration of CAR-T therapy for MM. A practical overview of the role of nursing professionals throughout all stages of CAR-T therapy administration for RRMM is provided., Conclusion: Planning, administration, and posttreatment monitoring for CAR-T therapy requires collaboration between nursing professionals and other healthcare providers as patients migrate between community oncology providers and specialized treatment centers. Nurses help with assessment of patient eligibility and patient and caregiver education before CAR-T therapy. They act in diverse roles across various settings involved in CAR-T therapy administration. Finally, nurses contribute to long-term identification and management of CAR-T-associated toxicities., Implications for Nursing Practice: Nurses are crucial to the CAR-T therapy process and make significant contributions to optimizing patient care and subsequent outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elizabeth Aronson reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Elizabeth Aronson has received honoraria from Janssen. Mary Steinbach reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Mary Steinbach is on the speakers bureau for Janssen, Karyopharm, and GSK. Laura Zitella reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Erika Florendo reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Erika Florendo is an employee of Legend Biotech and may hold stock and/or stock options in the company. Erin Lee reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Erin Lee is an employee of Janssen Research and Development and may hold stock and/or stock options in the company. Carrie Riccobono reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc. Carrie Riccobono is an employee of Legend Biotech and may hold stock and/or stock options in the company. Heather DiFilippo reports administrative support, article publishing charges, and writing assistance were provided by Janssen Pharmaceuticals Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease., Methods: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival., Results: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%)., Conclusions: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.)., (Copyright © 2023 Massachusetts Medical Society.)

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m 2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (<0.1%) by centralized flow cytometry and 84% (n = 16) successfully proceeded to hematopoietic stem cell transplant. Two-year overall survival was 75.6% [95%CI: 47.3%, 90.1%] for MRD-negative patients vs. 17.9% [95%CI: 4.4%, 38.8%] for those with residual disease (p < .001). Twelve subjects (34%) had known epigenetic alterations with 8 (67%) achieving a CR, 7 (88%) of whom were MRD negative. Correlative pharmacodynamics demonstrated the biologic activity of decitabine and vorinostat and identified specific gene enrichment signatures in nonresponding patients. Overall, this therapy was well-tolerated, biologically active, and effective in pediatric patients with R/R AML, particularly those with epigenetic alterations., (© 2022 Wiley Periodicals LLC.)

This qualitative study identified the parent health beliefs and normative beliefs related to child behavioral and mental health problems and examined the benefits and barriers of enrolling in an evidence-based parenting intervention among Filipino parents of school-aged children. A secondary aim was to also use the results to inform the development of a theory-based video intervention to increase enrollment in parenting interventions. Semi-structured interviews were conducted with fifteen parents who had or had not participated in the Incredible Years® parenting program, an evidence-based parenting intervention. Interviews were recorded and transcribed verbatim. Using a "Coding Consensus, Co-occurrence, and Comparison" methodology, emergent themes were mapped into a matrix against a priori-coded health belief model (HBM) and Theory of Planned Behavior (TPB) constructs. Parents believed that perceived susceptibility could be influenced by including knowledge of health disparities affecting Filipino youth in the U.S. Perceived severity was related to behavioral and mental health concerns about school, family dynamics, bullying and parent coping strategies. Perceived benefits included strengthening parent-child relationships, creating support systems, and learning positive parenting skills. Perceived barriers included logistics, stigma, and the perception of the relevance of the program, cultural factors such as generational differences about parenting, and family issues. Social norms and subjective norms related to parent participation were also discussed. Applying the HBM and TPB to enrollment in parenting interventions may explain low enrollment rates. Future interventions need to target perceived susceptibility to future behavioral health problems, barriers, and benefits to enrollment, and influence subjective and social norms., Competing Interests: Disclosure statement No potential conflict of interest was reported by the author(s).

Background: Supportive care improves outcomes in many cancers. In the pivotal STORM study selinexor, a first-in-class, oral, selective exportin 1 inhibitor, and low-dose dexamethasone proved to be an effective treatment for patients with triple-class refractory myeloma. We conducted a post-hoc analysis to test the hypothesis that increased utilization of supportive care measures in a sub-cohort of the STORM study prolonged treatment duration with- and improved efficacy of- selinexor., Materials and Methods: The STORM protocol included specific recommendations for dose modifications and supportive care to mitigate selinexor most common adverse events (AEs) including nausea, fatigue, and thrombocytopenia. The Tisch Cancer Center at Mount Sinai School of Medicine (MSSM) incorporated additional supportive care strategies within the framework of the STORM protocol., Results: Of 123 patients enrolled in STORM, 28 were enrolled at MSSM. The overall response rate was 26.2% in the overall STORM population and 53.6% in the MSSM cohort. Moreover, duration of response, progression free survival, and overall survival were longer in the MSSM cohort. AEs and dose modification events were similar in the 2 groups. The MSSM cohort had more dose reductions (67.9% vs. 50.5%), and higher use of multiple antiemetic agents (71.4% vs. 50.1%) and romiplostim (32.1% vs. 6.3%), but less discontinuations due to treatment-related AEs (3.6% vs. 25.3%)., Conclusion: These results suggests that in addition to more frequent dose reductions, prompter and more aggressive supportive care may have contributed to the low discontinuation rate, longer duration therapy, and greater efficacy rates observed in the MSSM cohort. (ClinicalTrials.gov NCT02336815)., Competing Interests: Disclosure A.C. receives research funding from: Janssen, Celgene, Novartis Pharmaceuticals, Amgen, Pharmacyclics, Seattle Genetics, Millenium/Takeda and has a consulting/advisory role at: Janssen, Celgene, Novartis Pharmaceuticals, Amgen, Bristol Myers Squibb, Karyopharm, Sanofi Genzyme, Seattle Genetics, Oncopeptides, Millenium/Takeda, Antengene, Glaxo Smith Kline Secura Bio; E.F. is part of the speakers bureau for: Karyopharm, Bristol Myers Squibb, Takeda and has an advisory role at: Janssen; S.I.M. none; H.C. received commercial research support from Genentech Roche, Celgene, and Takeda outside the submitted work, and is employed by the Multiple Myeloma Research Foundation in a capacity that does not conflict with the submitted work; D.M. has a consulting/advisory role at: Janssen, Celgene, Takeda, Legend, GSK, Foundation Medicine, Abbvie; S.P. has a consulting role at Foundation Medicine and receives research funding from: Celgene, Karyopharm; J.R. is part of the speakers bureau for: Celgene, Janssen and has a consulting/advisory role at: Celgene, Janssen, Karyopharm, Antengene, Oncopeptides, X4 pharmaceuticals, Adaptive biotechnologies, SecuraBio, Sanofi; A.D. None; J.T. None; G.J. None; A.L. None; S.B. None; S.J. has a consulting role at: AbbVie, Bristol Myers Squinn, Janssen, Karyopharm, Merk & Xo., (Copyright © 2021. Published by Elsevier Inc.)

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4-5 months. Previous studies explored addition of weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study of pomalidomide, daily cyclophosphamide and weekly dexamethasone (PCD). Thirty-three patients were evaluable for efficacy and underwent 28-day cycles of pomalidomide (4 mg/day, D1-21), cyclophosphamide (50 mg b.i.d., D1-21) and weekly dexamethasone. All were lenalidomide-refractory and 55% were refractory to lenalidomide and proteasome inhibitor. ORR was 73%; median PFS and overall survival were 13.3 months and 57.2 months respectively. Grade 3/4 toxicities were primarily hematologic but manageable with dose reductions. Early disease progression correlated with MYC expression and flow cytometry demonstrates an activated microenvironment post-PCD. Addition of metronomic cyclophosphamide to pomalidomide and dexamethasone is a cost-effective, oral regimen with encouraging PFS.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (<90 days) PFS to therapy. MAGEA1 RNA and protein expression were correlated with short PFS, and laboratory studies demonstrated a role for MAGE-A in resistance to panobinostat-induced cell death. FRD demonstrates durable responses, even in high-risk, lenalidomide-refractory patients, indicating the essential role of panobinostat in attaining responses. MAGEA1 expression may represent a functional biomarker for resistance to panobinostat. In contrast to PANORAMA 1, there were no significant GI toxicities and primarily expected hematologic toxicities. This trial was registered at www.clinicaltrials.gov as #NCT00742027., Competing Interests: Conflict-of-interest disclosure: The following authors have served as paid consultants for the identified companies: A.C. for Novartis and Celgene; S.J. for Novartis and Celgene; and D.C. and D.V. for Celgene speakers bureau. The remaining authors declare no competing financial interests.