Cappelleri, Joseph C.

Abstract Background Patients’ self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials. Methods A systematic search of PubMed, Web of Science, and Embase was performed using predefined eligibility criteria. Thirty-one literature reviews and 3 clinical practice guidelines met inclusion criteria and were selected for review and data abstraction. Results Findings from this scoping review demonstrated several leading sympAEs that were reported across immunotherapy and targeted therapy drugs, including fatigue, diarrhea, and rash. In addition to these more prevalent sympAEs, there were some less frequently reported class-specific sympAEs, which had potential for significant harm or disability to the patient if not properly identified and treated. Many studies reported toxicities as AEs or syndromes solely using data reported by clinicians without additional self-report from patients. Conclusion We identified several core sympAEs experienced by patients participating in oncology trials using immunotherapy and targeted therapy agents, which has implications for future trial design and drug labeling. Future cancer trials should assess patient-reported sympAEs based on the identified drug mechanism to inform the tolerability of these newer agents and enhance patient safety during trial participation and clinical care.

BACKGROUND Several studies have highlighted the poor clinical outcomes observed among patients with relapsed/refractory multiple myeloma (MM), particularly those with triple-class refractory (TCR; refractory to at least one protease inhibitor [PI], one immunomodulatory drug [IMiD], and one anti-CD38 monoclonal antibody [mAb]) disease. The aim of this study was to describe the longitudinal changes in quality of life (QOL) and other patient-reported outcomes (PROs) among TCR MM patients who initiated a new line of therapy in real-world clinical practice. METHODS A prospective, multi-site observational study was conducted through the Mayo Clinic system. Patients with TCR MM initiating a new line of therapy (defined as the index date) were followed for a 12-month observation period. For patients initiating a CAR-T therapy, PRO survey assessments were conducted at apheresis, lymphodepletion chemotherapy, and every month after T-cell infusion until Month 6. All other patients received a survey assessment before index and every month thereafter until Month 6. PRO measures included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30; including the Global Health Score [GHS]), the EORTC Multiple Myeloma Questionnaire (QLQ-MY20; including the Disease Symptoms [DS] domain score), the EORTC QLQ for Chemotherapy-Induced Peripheral Neuropathy (CIPN20), the EuroQoL-5 Dimensions (EQ-5D), the Patient Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). PRO surveys were supplemented with retrospective chart reviews conducted at 3 months and 12 months following the index date to obtain clinical information. Descriptive data were reported at each timepoint separately for patients who received CAR-T and non-CAR-T index therapies. The study is ongoing and this abstract reflects all patient data collected as of May 2024. RESULTS This interim analysis included 77 patients (58% male, 95% White, mean age 66 years). The median time interval between becoming TCR and the index date was 5.6 months (interquartile range [IQR]: 1.8, 18.2). Most patients had an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (48% and 45%, respectively) and were Revised International Staging System (R-ISS) I or II (27% and 36%, respectively); 42% of patients had high-risk cytogenetics and 14% had extramedullary disease. The median (IQR) number of prior treatment lines was 4 (4, 5). Forty-two patients initiated a CAR-T therapy as their index therapy (12 and 30 treated with ide-cel and cilta-cel, respectively); the remaining 35 patients predominantly initiated a treatment regimen containing an IMiD (51%), a PI (54%), an anti-CD38 antibody (40%), or an alkylating agent (37%). Among these non-CAR-T patients, common regimens used were pomalidomide + elotuzumab + corticosteroids (26%), carfilzomib + cyclophosphamide + corticosteroids (20%), and pomalidomide + carfilzomib + corticosteroids (17%). Among CAR-T patients, QOL generally remained stable from apheresis (mean GHS and EQ-5D VAS were 62.3 and 66.4, respectively) to lymphodepletion (61.2 and 65.9) to Month 6 (64.2 and 68.9). Disease symptoms improved (mean DS domain scores at apheresis, lymphodepletion, and Month 6 were 25.7, 24.1, and 20.1, respectively) though pain, specifically, plateaued/worsened (mean pain domain scores were 24.5, 32.1, and 32.6). Based on the PGIC, 76% of patients reported being “a little better” or “much better” as early as Month 1, which stabilized over time (75% at Month 6). Among non-CAR-T patients, QOL largely remained stable (GHS and EQ-5D VAS was 62.9 and 68.4, respectively, at baseline and 64.9 and 67.7 at Month 6), though disease symptoms, including pain, improved over time (DS was 28.0 at baseline and 22.8 at Month 6; pain was 40.8 at baseline and 28.1 at Month 6). Based on the PGIC, 30.7% of patients reported being “a little better” or “much better” at Month 1, which improved to 52.7% by Month 6. CONCLUSIONS In this interim analysis of an ongoing prospective observational study, baseline values suggest a significant QOL burden among TCR patients. QOL generally remained stable for both CAR-T and non-CAR-T patients over the first several months post-therapy with some select improvements in disease symptoms. However, the patients (particularly CAR-T patients) directly reported some holistic improvement based on the PGIC as early as Month 1.