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4543 Post Autologous Stem Cell Transplant Maintenance in Patients with Newly Diagnosed Multiple Myeloma: A Network Meta-Analysis

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Syed Arsalan Ahmed Naqvi, MBBS1*, Sarosh Fatima, M.B.B.S2*, Noureen Asghar3*, Hafsah Ijaz, M.B.B.S.4*, Ahsan Ayaz, M.D.5*, Huan He, Ph.D.6*, Muhammad Husnain, MD7*, Rajshekar Chakraborty, MD8, Irbaz Riaz, MD, MMSc9 and Mohammed A. Aljama, M.D.10*

1Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ
2Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
3Creighton University, Omaha, NE
4Nishtar Medical University, Multan, Pakistan
5Mayo Clinic, Phoenix, AZ
6Mayo Clinic, Rochester, MN
7University of Arizona Cancer Center, Division of Hematology and Medical Oncology, Tucson, AZ
8Hematology and Medical Oncology, Columbia University, Irving Medical Center, New York, NY
9Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
10McMaster University, Hamilton, ON, Canada


The therapeutic paradigm for newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplant (ASCT) is evolving. Emergence of newer maintenance therapies has prompted this network meta-analysis to assess the comparative effectiveness of available options using the most up-to-date evidence, and thereby informing optimal therapy in this setting.


MEDLINE and EMBASE were comprehensively searched using a systematically structured search strategy to identify phase II/III randomized controlled trials (RCTs) assessing contemporary maintenance therapies in NDMM patients undergoing ASCT. The main outcomes of interest included progression-free survival (PFS) and overall survival (OS). Precomputed hazard ratios (HR) with 95% CI were pooled using an inverse variance approach. Incidence rate ratios were computed for trials not reporting HR. Mixed treatment comparisons were made using a network meta-analytic approach within the frequentist framework. Relative treatment rankings were evaluated using P-scores (PS) and were interpreted in congruency with pairwise estimates. Higher ranks indicated better efficacy.


As of 25th July 2022, 16 RCTs with 12 unique treatment arms, and 14 RCTs with 10 unique treatment arms, contributed to the network of PFS and OS outcomes, respectively. Mixed treatment comparisons showed that the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) and KR were associated with significantly improved PFS when compared to lenalidomide (Len) maintenance (KRd vs. Len - HR: 0.56; 95% CI: 0.34-0.93, KR vs. Len - HR: 0.64; 0.44-0.94), daratumumab (Dara) (KRd vs. Dara - HR: 0.53; 0.30-0.93, KR vs. Dara – HR: 0.60; 0.38-0.96), thalidomide-steroid (Thal-Steroid) (KRd vs. Thal-Steroid: HR - 0.49; 0.28-0.84, KR vs. Thal-Steroid - HR: 0.56; 0.36-0.86), Thal (KRd vs. Thal - HR: 0.40; 0.23-0.69, KR vs. Thal - HR: 0.46; 0.30-0.71), and ixazomib (Ixa) maintenance (KRd vs. Ixa - HR: 0.39; 0.22-0.68, KR vs. Ixa – HR: 0.44; 0.28-0.69). Although there was a signal of potential PFS benefit with KRd and KR when compared to Ixa, lenalidomide, and dexamethasone (IRd), the difference was not statistically significant (KRd vs. IRd - HR: 0.68; 0.34-1.32, KR vs. IRd – HR: 0.77; 0.43-1.39). The results were consistent for KRd and KR as compared to Len-Steroid (KRd vs. Len-Steroid – HR: 0.67; 0.36-1.23, KR vs. Len-Steroid – HR: 0.76; 0.45-1.28). However, KRd and KR were not significantly different from each other. Ranking analysis showed KRd (PS: 0.95; rank 1) and KR (PS: 0.91; rank 2) were potentially the most efficacious with regards to PFS benefit followed by IRd and Len-Steroid (PS: 0.75, rank 3), Len (PS: 0.63; rank 5), Dara (PS: 0.57; rank 6), Thal-Steroid (PS: 0.49; rank:7), Thal (PS:0.30; rank: 8), and Ixa (PS: 0.28; rank: 9). Len maintenance was associated with significantly improved PFS compared to Ixa (HR: 0.69; 0.55-0.88), and Thal (HR: 0.72; 0.59-0.88) as shown in Figure 1A. Mixed treatment comparisons for OS outcomes showed a consistent pattern of benefit with KR when compared to Thal (HR: 0.40; 0.19-0.86), Thal-Steroid (HR: 0.46; 0.21-0.99), and Len-Steroid (HR: 0.35; 0.13-0.94). Although, there is a signal of OS benefit with KR when compared to Len, the effect is not statistically significant (HR: 0.54; 0.26-1.12). Similarly, while the direction of effect indicated potential OS benefit with KRd as compared to Thal, Thal-Steroid, and Len-Steroid, the difference was not statistically significant. No statistically significant associations were observed for other mixed treatment comparisons with regards to OS at the current follow up of the included trials as shown in Figure 1B. Sensitivity analyses limited to phase III RCTs showed consistent results.


Maintenance therapy with KRd and KR may prolong PFS compared to other therapies including Len, Thal, Ixa, and Dara maintenance but not when compared to Len-Steroid and IRd. Overall survival data is still emerging and results at longer-follow up with subgroup analyses by age, prior response status, and cytogenetic risk profiles are warranted and may offer additional insights. Thus, a living systematic review is being maintained and these results will be updated as soon as new data becomes available.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH