MYC Status Relevant to Risk Stratification in Newly Diagnosed Multiple Myeloma

In evaluating MYC rearrangement and its correlation with disease burden and prognostics in newly diagnosed multiple myeloma, a group of Mayo Clinic investigators found that the alteration is associated with high disease burden and independently prognosticates adverse outcomes in patients.

The study was a retrospective analysis of database information on patients with multiple myeloma treated in the real-world setting. Prior to this study, the prognostic value of MYC had not been established, but such understanding is needed in the field considering the commonality of MYC rearrangements in this patient population.

A total of 1342 patient records were retrospectively reviewed from patients treated at the Mayo Clinic in Rochester, Minnesota from January 2006 through January 2018. These patients were newly diagnosed with multiple myeloma by fluorescence in-situ hybridization (FISH). Testing for MYC was conducted with the break apart FISH probe at baseline, at which time it was determined that 111 patients (8%) had an MYC rearrangement.

Patients were treated with either a proteasome inhibitor (PI)-based therapy, an immunomodulatory agent (IMiD), or a combination of both a PI-based therapy and IMiD. The 2 PI-based regimens used were bortezomib (Velcade)-containing combinations (n = 373), or ixazomib-containing regimens ([Ninlaro], n = 38) . The IMiD regimens contained lenalidomide ([Revlimid], n = 411) or thalidomide ([Thalomid], n = 18). Finally, the regimens combining PIs and IMiDs that some patients received included bortezomib plus lenalidomide (n = 358), carfilzomib plus lenalidomide (n = 27), bortezomib plus thalidomide (n = 11), ixazomib plus lenalidomide (n = 8), and carfilzomib plus thalidomide (n = 7).

Among the population of patients with newly diagnosed multiple myeloma and an MYC rearrangement, no differences in overall response rates (ORRs) were observed. Patients who were treated with either bortezomib combination or ixazomib combination achieved ORRs of 76% vs. 80%, respectively (P =.53). Those treated with the IMiD regimens of either lenalidomide or thalidomide had ORRs of 91% vs. 82%, respectively (P =.02). In terms of combination therapy with a PI and IMiD, the ORR was 88% compared with 95% (P =.13).

The achievement of very good partial responses (VGPRs) was were assessed in the study and showed that the presence of MYC rearrangement led to fewer VGPRs compared with those who did not have MYC rearrangements in the population treated with a PI plus an IMiD. No significant difference in VGPR rates in patients treated with the PI-based regimens compared with the IMiD-based regimens. The VGPRs rate were 35% vs. 60% for PI-based regimens (P =.73), 36% vs. 29% for IMiD-based regimens (P =.33). It was also notable that all patients who underwent post-induction transplant had a PR to treatment and 85% of those treated with PI-containing regimens versus 80% of those treated with IMiD-containing regimens, regardless of MYC rearrangement status (P =.54).

In terms of survival, it appeared that MYC rearrangement led to significantly shorter overall survival (OS) in patients with multiple myeloma. The median OS observed in patients with MYC rearrangement was 5.3 years (95% CI, 4.4-6.1) compared with 8.0 years (95% CI, 6.9-8.9) in patients who did not have MYC rearrangements (P <.0001).

Notably, MYC rearrangements in patients with multiple myeloma were associated with increased mortality compared to absence of MYC rearrangements with a risk ratio of 1.7 (95% CI, 1.3-2.2; P <.001).

Looking at characteristics of patients gathered at baseline, it was also revealed that the presence of MYC rearrangements versus the absence of MYC rearrangements was indicative of elevated β2-microglobulin (71% vs. 58%; P = .01), respectively. MYC rearranged multiple myeloma also led to more than 50% bone marrow plasma cells (70% vs. 54%; P =.003), respectively, as well as lytic lesion (78% vs. 58%; P =.04), and immunoglobulin G multiple myeloma (35% vs. 24%; P =.0006).

It was determined based on these real-world data that MYC rearrangements may play a role in risk stratification of patients with newly diagnosed multiple myeloma.

_Reference:

_{Abdallah N, Baughn LB, Rajkumar SV, et al. Implications of MYC rearrangements in newly diagnosed multiple myeloma. Clin Can Res. Published online October 2, 2020. doi: 10.1158/1078-0432.CCR-20-2283}