Impact of Autologous Stem Cell Transplant (ASCT) Versus Consolidation on Health-Related Quality of Life (HRQoL) for Patients with Multiple Myeloma Receiving Carfilzomib Maintenance: Results from the Cardamon Trial

Introduction: The role of front line ASCT remains under evaluation with the incorporation of highly effective induction and salvage strategies. The Cardamon trial investigated if patients receiving a Carfilzomib based regimen could safely defer ASCT. We previously reported that Carfilzomib (K) Cyclophosphamide (C) Dexamethasone (d) consolidation (cons) was marginally not non-inferior to ASCT. Aside from efficacy, HRQoL may assist in evaluating the overall benefit of ASCT. Here we report the HRQoL of patients on both arms and the impact of ASCT on the tolerability of maintenance.

Methods: Newly diagnosed transplant-eligible (NDTE) pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40 mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons. All received 18 months K maintenance (56mg/m2 D1,8,15). HRQoL was measured by EQ-5D, EORTC QLQ-C30 and QLQ MY20 questionnaires completed at registration, post-peripheral blood stem cell harvest (PBSCH), post-randomised treatment (day 100 post-ASCT/end of KCd cons) and 6 months maintenance. We used linear regression to assess treatment effect on the change in QoL between two timepoints with adjustment for values at the earlier timepoint. A paired t-test was used to examine changes in HRQoL from registration to post-PBSCH. To account for multiple testing, p-values ≤0.01 were considered significant.

Results: Updated analysis continued to demonstrate that KCd cons was not non-inferior to ASCT (2-year PFS 75% (ASCT) vs 68% (KCd cons) and calculated difference -7.2% (70% CI -11.1% to -2.8%), which just exceeded the non-inferiority margin of -10%. Compliance with Patient Reported Outcome questionnaires was 63%, with a total of 176, 142, 123 and 104 patients providing data at registration, post-PBSCH, post-randomised treatment and at 6 months maintenance respectively. Baseline scores demonstrated low global health status (mean 61.3, SD 24.4) and social functioning (mean 60.9, SD 36.5), reflecting the impact of newly diagnosed myeloma.

Following completion of KCd induction and PBSCH, significant improvements were reported in physical functioning (+4.9, p=0.01), pain (-9.9, p=0.001), constipation (-7.8, p=0.01), future perspective (+12.2, p<0.001) and the EQ5D functional scales (single index utility +0.05, p=0.004; visual analogue scale +5.9, p=0.002). However, body image (-13.2, p<0.001) and financial difficulties (+11.2, p<0.001) worsened significantly with no improvement in fatigue (-1.4, p=0.6).

Changes between post-PBSCH and post-randomised treatment in global health status, functional and most symptom scales were minimal and similar between treatment arms, however patients in the ASCT arm were less likely to improve on disease symptoms (MY20) (difference in change from post-PBSCH, KCd cons vs ASCT, -8.0, p=0.003) and pain (-11.3, p=0.008). This may reflect ASCT's increased treatment intensity, given the higher MRD negativity rates (30.3% KCd cons vs 47,7% ASCT, p=0·008), with incomplete recovery causing delayed symptom improvement at ASCT Day 100.

From post-randomised treatment to 6 months maintenance, patients in the KCd cons arm were less likely to experience a decline in cognitive and social functioning (difference in change from post-randomised treatment, KCd cons vs ASCT, cognitive +7.3, p=0.007; social +16.1, p<0.001) and were less likely to experience financial difficulties (-16.5, p=0.002) compared to those in the ASCT arm. This may be related to a higher incidence of grade 3+ events during K maintenance for ASCT (64.6%) compared to KCd cons (45·4%) (p=0.01). This difference was driven by a higher proportion of grade 3+ lung infections and cytopenias in the ASCT arm. Additionally, withdrawals due to adverse events or patient/clinician decision were more common in the ASCT arm (6·2% KCd cons vs 16·2% ASCT, p=0·03).

Conclusions: Our results confirm an improvement in symptoms and functional HRQoL after completing induction therapy, but some aspects of social and financial function remain poor, and fatigue persists. The adverse effects of ASCT on HRQoL may still be evident at 3 months post ASCT. K maintenance was less well tolerated for those receiving ASCT than KCd cons, and this also impacted HRQoL, suggesting a tradeoff for the efficacy advantages. The impact of ASCT on HRQoL during and after the transplant should be considered when assessing the benefit of ASCT over cons for patients.

Popat:GSK: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria; Janssen, Takeda, GSK: Other: Travel expenses from Janssen, Takeda, GSK; Janssen, Takeda, Celgene, and GSK: Honoraria; Takeda: Research Funding; Takeda, AbbVie, GlaxoSmithKline, and Celgene: Consultancy; BMS: Honoraria. Benjamin:Bristol Myers Squibb/Celgene: Research Funding; Amgen: Research Funding. Chapman:Sanofi: Honoraria. Clifton-Hadley:Astra Zeneca, GSK, Pfizer, MSD, BMS, Amgen, Millennium Takeda: Other: CRUK and UCL CTC have received research funding in the past 24 months, Research Funding. Owen:Astra-Zeneca: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Front line use of carfilzomib for myeloma