Hydren, Jay R.

Introduction: Light-chain amyloidosis (ALA) is a rare plasma cell disorder characterized by multiorgan involvement. Patients often present with non-specific symptoms, which can lead to a delay in diagnosis. This is associated with progressive organ involvement and shorter survival. Reducing the time from symptom onset to diagnosis is a critical step in improving outcomes. This study was designed to evaluate the clinical prodrome and challenges associated with the diagnosis of ALA from the patient perspective. Methods: This retrospective study surveyed patients with ALA through the online HealthTree® Cure Hub platform, which helps patients navigate their disease in a holistic way. The survey consisted of 32 questions, including 23 multiple-choice, 7 date-entry, and two free-response questions. Data on diagnosis and demographics were extracted from the electronic health record and self-reported data linked to HealthTree® Cure Hub. Results were reported as numbers and percentages, and comparisons were made by age (≥70 vs. <70 years) and sex. The following statistical methods were used: Fisher's exact test for categorical data, two-sample t-test and F-test for normally distributed continuous data, Wilcoxon rank-sum test for skewed data and Spearman correlation coefficient. Results: We surveyed 248 patients. Of those, a total of 87 patients with a self-reported diagnosis of ALA completed the questionnaire between March 12, 2023, and May 8, 2024. The median age was 66 years; 55% were female, and 91% were white. The most common initial symptoms prompting patients to seek medical evaluation were fatigue/weakness (47%), swelling (38%), shortness of breath (28%), chest pain (23%), and foamy urine (22%). Pain in hands/feet, carpal tunnel syndrome, loss of appetite, hoarseness, macroglossia, diarrhea, periorbital puffiness, nail changes, and erectile dysfunction each accounted for <10% of cases. Signs and symptoms were first detected by patients themselves in 58% of cases, by a physician in 33% and by a family member or friend for the rest. The median number of symptoms per individual was 2; 31% reported only one symptom, 37% 2-3, 18% 4-6, and 14% >6; with chest pain being the most common (39%), followed by swelling (22%), shortness of breath (13%), and foamy urine (13%); one patient reported erectile dysfunction and another reported arrhythmias as their only symptom. There was a correlation between hoarseness and nail changes (ρ=0.71), and carpal tunnel syndrome and orthostatic hypotension (ρ=0.63). Only 16% were aware of ALA as a condition prior to symptom onset. Thirty six percent presented to a general practitioner for initial evaluation; about 50% sought a specialist, including a myeloma/amyloid specialist (21%), and 14% were first evaluated in the emergency department. While most patients (45%) were diagnosed by a hematologist/oncologist, patients reported seeing a median of 3 physicians (range: 1-10) before the diagnosis was established. Among responders, 61% reported having myeloma at the time of testing. After diagnosis, about 50% were referred to a center specialized in ALA, and 72% met with a stem cell transplant specialist. Most patients reported receiving multidisciplinary care, with a median of 3 additional specialists participating in ALA care (range: 0-16). More than half of patients (59%) felt the diagnosis was delayed; among those, 42%, 24%, 24%, and 11% reported a delay of 1-6, 7-12, 13-24, and >24 months, respectively. The proportion of patients reporting >12-month delay was higher among older patients (54% vs. 27%, P=0.02). A quarter of responders felt their treatment was delayed. Half of patients felt the diagnostic delay contributed to a decrease in treatment efficacy and 48% did not feel that all medical professionals were knowledgeable about ALA. Only 38% felt the diagnostic process was simple and easy within their healthcare system. Conclusion: Most patients with AL amyloidosis initially present with non-specific symptoms, with fatigue/weakness being the most common. Over a third were evaluated first by a general practitioner, and about a third reported a diagnostic delay of >12 months. The diagnostic process is associated with high healthcare utilization, even among patients with concurrent multiple myeloma. Increasing disease awareness among patients and medical providers may shorten the time to diagnosis and contribute to improved outcomes.

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.