Patel, Saurabh N.

Introduction Talquetamab (Tal) is a bispecific antibody therapy approved for patients with relapsed/refractory multiple myeloma (MM), targeting both GPRC5D x CD3 receptors. Clinical studies demonstrate that Tal creates deep and durable responses, but less is known about the patient experience. This study aimed to explore the experiences of patients from the patient and physician perspectives to help understand what to expect with this first-in-class novel therapy. Methods This qualitative study consisted of two components. First, patients with documented use of Tal were identified and recruited through the HealthTree Cure Hub. Individual patients then took part in 2-hour, semi-structured virtual interviews. Patients were asked to discuss their experiences 1-2 months prior to starting Tal and 4-5 months after beginning therapy. Patients discussed GPRC5D-related symptoms (including oral, skin-related, and nail-related symptoms), overall impact, and satisfaction. Participants were US adults diagnosed with MM who took Tal for at least 4 months, either in a clinical trial or commercial setting. Interviews were conducted February-April 2024. Second, patients and physicians gathered in a facilitated roundtable discussion to review findings and generate ideas for symptom management. The roundtable lasted 2.5 hours and took place in Chicago, IL in May 2024. Results Eight men and 4 women (n=12) aged 52-79 years participated in the interviews. Interviewed participants were mostly white (84%) and college-educated (84%). Seven (58%) received Tal in a clinical trial, and 9 were still receiving Tal. Roundtable participants included 3 patients (2 male, 1 female; all white and college educated), and 3 physicians with Tal experience. In the interviews, patients reported high overall satisfaction, with most (75%) rating their satisfaction an 8 or higher on a 10-point scale. Satisfaction was largely driven by the effectiveness of therapy, with all reporting clinical improvements in their MM disease. Patients reported improvements in their energy/strength and decreased fatigue. They also reported increased physical activities and ability to work, volunteer, or engage in hobbies. Physicians affirmed these findings as consistent with their observations and noted they are also very satisfied with Tal. Oral symptoms such as distorted taste/loss of taste and dry mouth were common with varying severity. Although all interviewees (n=12) reported taste symptoms (typically starting within the first month of therapy), five said their symptoms fully improved (3 after 1 year on treatment, and 2 after stopping treatment), and 4 experienced partial recovery. Ten lost weight, but most (92%) maintained adequate nutrition. Patients and physicians suggested coping strategies including diet modifications, use of strong flavors (e.g., spices, cinnamon), monitoring weight, prioritizing adequate calories, using mouthwashes/lozenges, drinking water while eating, taking small bites, and consuming foods that are easier to swallow. They also noted that it is important to educate patients on expected symptoms before starting the treatment. Skin- and nail-related symptoms were also common but less impactful on quality of life. All patients (n=12) experienced skin- and nail-related symptoms, but most considered these symptoms mild. Skin-related symptoms such as dry skin and skin exfoliation occurred once and typically lasted 1-2 months. Nail symptoms were primarily cosmetic, and the duration varied. Suggested management strategies include skin moisturizers, nail thickeners/hardeners, keeping nails short, and wearing protective gloves. Physicians noted it's helpful to reassure patients that nail loss is not harmful. Overall, GPRC5D-related symptoms were not treatment-limiting, and no patients had to miss a dose due to these symptoms. Patients perceived these symptoms as bearable but noted the treatment was effective at controlling the disease. Conclusions This study described patient experiences and reflected how patients perceive the benefit/risk profile of talquetamab. Symptoms were perceived as bearable and high satisfaction scores were driven by strong clinical effectiveness. Patients and physicians agreed that real-world feedback from patients, practical tips, and management strategies are vitally important for patients and physicians using this novel therapy.

Introduction: Despite the development of advanced treatment options, multiple myeloma (MM) remains an incurable disease. Most MM patients relapse and require further treatments. B-cell maturation antigen (BCMA) targeted immunotherapy is a novel MM therapy class that is now available to heavily pre-treated relapse/refractory MM (R/R MM) patients, who were triple class exposed (TCE) to proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. As BCMA therapies continue to be further utilized and become an integral part of MM treatment, the proportion of TCE patients who are also BCMA exposed (TCE+BCMA exposed) is expected to grow. However, the clinical outcomes of TCE+BCMA exposed RRMM patients have not been previously assessed. The objective of this study was to evaluate the real-world outcomes of TCE+BCMA exposed MM patients who started a subsequent LOT, describing their characteristics, treatment patterns, and clinical outcomes. Subgroups of penta-drug exposed (at least two PIs, at least two IMiDs, and at least one anti-CD38) patients, as well as White and African American patients were also evaluated as penta-drug exposure status and race were known to impact clinical outcomes. Methods: Adult patients with MM who were TCE+BCMA exposed and started a subsequent LOT starting from July 03, 2019 (when additional new treatment options became available) were selected from the Komodo Healthcare Map (a US claims dataset) and were followed until the earliest of death, last claim, or end of study period (December 31, 2022). Index date was defined as the start date of the subsequent LOT following TCE and BCMA exposure. Descriptive statistics were provided for patient characteristics and treatment patterns. Clinical outcomes including time to treatment discontinuation or death (TTD) and time to next treatment or death (TTNT) were estimated using the Kaplan-Meier method. Results: A total of 344 TCE+BCMA exposed patients, who received the next LOT were included in the study, including 152 (44.2%) patients who were penta-drug exposed before index, 57 (16.6%) African American, and 185 (53.8%) White patients. Key baseline demographic characteristics and treatment history for the overall group and the three subgroups are listed in Table 1. The mean (SD) and median number of prior LOTs for the overall group before index date were 5.7 (1.7) and 6.0, respectively. The most prevalent prior treatments before the index date for the overall group were daratumumab (99.1%), belantamab mafadotin (91.9%), pomalidomide (84.3%), carfilzomib (83.1 %), bortezomib (76.2%) and lenalidomide (72.1%). Excluding corticosteroids, the most frequently used index treatments (i.e., treatment used post TCE+BCMA exposure) were carfilzomib- (21.9%), bortezomib- (20.8%), pomalidomide- (18.3%), and belantamab mafadotin- (18.3%) based regimens. The median (95% confidence interval [CI]) TTD was 3.7 (3.3, 4.4) months, and the median (95% CI) TTNT was 6.4 (5.5, 7.6) months. TTD and TTNT estimates for the three subgroups are listed in Table 2. Conclusions: To our knowledge, this is the first real-world study of treatment patterns and outcomes for TCE+BCMA exposed MM patients who started a subsequent LOT. The findings showed that this group of heavily pretreated MM patients were often retreated with the same therapies or therapies in the same classes, as they have limited effective treatment options. TCE+BCMA exposed patients exhibited poor clinical outcomes, as demonstrated by the rapid treatment discontinuation and moving on to the next treatment shortly after initial treatment. Many patients were already penta-drug exposed, and they appear to have worse clinical outcomes than the overall patient group. A shorter TTD was observed, and a trend for shorter TTNT was observed among African American patients than White patients. The findings highlight the continued need for effective treatments for heavily treated MM patients and particularly those with poor outcomes.