Health‐related quality of life in patients with light chain amyloidosis treated with bortezomib, cyclophosphamide, and dexamethasone ± daratumumab: Results from the ANDROMEDA study

Abstract

In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D‐VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient‐reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated‐measures, mixed‐effects model. The magnitude of changes in PROs versus baseline was generally low, but between‐group differences favored the D‐VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D‐VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D‐VCd group versus the VCd group. After cycle 6, patients in the D‐VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health‐related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent‐to‐treat population. These results demonstrate that the previously reported clinical benefits of D‐VCd were achieved without decrement to patients' HRQoL and provide support of D‐VCd in patients with AL amyloidosis.

Is there a representative quality‐of‐life questionnaire for patients with AL amyloidosis?—systematic literature review

“…The QoL of transplant‐ineligible patients, achieving very good partial response//CR, improves steadily up to 2 years after treatment but remains lower than that of the population norm. Improvement of QoL is, also, associated with a survival benefit 9,10 …”

“…The arsenal of therapeutic options for AL amyloidosis has increased in recent years and QoL improvement has become recognised by regulatory authorities as important and required for drug approval. Nevertheless, there is no consistency in the QLQs used between the various trials, with some referring to more than one 10–14 …”

“…Nevertheless, there is no consistency in the QLQs used between the various trials, with some referring to more than one. [10][11][12][13][14] QoL outcomes have been explored in clinical trials. Patients that received daratumumab-bortezomibcyclophosphamide-dexamethasone (Dara-VCD) reported more rapid and long-lasting improvement compared with those that received VCD and clinically meaningful differences were observed after at least 6 months of treatment.…”

“…Patients that received daratumumab-bortezomibcyclophosphamide-dexamethasone (Dara-VCD) reported more rapid and long-lasting improvement compared with those that received VCD and clinically meaningful differences were observed after at least 6 months of treatment. 10 In the EMN-03 trial that compared bortezomib-melphalandexamethasone (VMD) to melphalan-dexamethasone (MD) alone, the addition of Bortezomib did not affect the QoL of the patients. 13 Gillmore et al showed that cyclophosphamidethalidomide-dexamethasone provided higher early CR rates to MD without additional QoL burden.…”

Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib‐dexamethasone versus physician's choice

“…Nonetheless, on the FACT/GOG-Ntx, small but significant improvements in neurotoxicity and sensory summary scores, as well as seven individual items, were observed in favor of ixazomib-dexamethasone relative to PC. It is possible that these measures may not be sufficiently sensitive to detect symptom burden or true decrements in underlying disease in patients with relapsed/ refractory AL amyloidosis.A prior analysis of PROs from the phase 3 ANDROMEDA trial evaluating daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) versus VCd alone with newly diagnosed AL amyloidosis found that patients with clinical improvement following systemic therapy for AL amyloidosis experience small but meaningful improvements in HRQOL and symptoms 14. During treatment, score changes from baseline in PRO measures including the SF-36, EQ-5D, and EORTC QLQ-C30, albeit small in magnitude, generally favored D-VCd over VCd alone 14.…”