Outcomes Have Improved Over Time in Myeloma Patients Relapsing Early After ASCT

Angela Dispenzieri, MD

Rates of early relapse post-autologous stem cell transplant (ASCT) in patients with relapsing multiple myeloma have not changed over time, but post-relapse survival among early relapsers has improved for patients transplanted after 2005 and for those relapsing since 2008.

In an analysis of patients enrolled in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, the proportion of patients relapsing within 2 years has remained stable at slightly more than one-third over 3 time periods (2001-2004, 2005-2008, and 2009-2013), reported Angela Dispenzieri, MD, at the 2017 BMT Tandem Meetings.

Patients transplanted in the latter 2 periods had significantly better post-relapse survival at 1 year, 2 years, 3 years, and 5 years compared with those transplanted from 2001 to 2004 (P = .006).

Patients who relapsed at 2008 or later had a 72% 1-year post-relapse survival compared with 61% for those who relapsed before 2008. Two-, 3-, and 5-year post-relapse survival was 55%, 43%, and 26% in patients who relapsed at 2008 or after, compared with 45%, 33%, and 21% among those who relapsed before 2008 (P <.01).

“These data seem to suggest that it was not so much when you were transplanted but really when you relapsed…if you were one of those patients who relapsed early,” said Dispenzieri, from the Bone Marrow Transplant Program at Mayo Clinic, Rochester, Minnesota.

Included in the analysis were patients from the CIBMTR registry who received a single ASCT between January 2001 and December 2013. Eligible patients had to have ASCT within 12 months of diagnosis and were required to have >100 days of post-transplant follow-up. For the purpose of analyzing relapse-free survival, patients had to have at least 4 years of post-ASCT follow-up.

Patients diagnosed during each period had a similar median age at transplant, similar Karnofsky scores, and similar renal function. During the most recent period, the proportion of patients with advanced MM was lower (30%) compared with 2005 to 2008 (38%) and 2001 to 2004 (43%).

“What really was different was how patients were managed,” Dispenzieri said. Induction during the earliest period was mostly with “VAD [vincristine, Adriamycin, and dexamethasone] types of regimens and very little in terms of novel therapies” whereas during the most recent period, almost 70% of patients received lenalidomide, bortezomib, and dexamethasone or another triplet as induction. The maintenance strategy was overwhelmingly no maintenance during 2001 to 2004, whereas during 2009 to 2013, the vast majority received maintenance therapy with novel agents and only a small fraction did not receive maintenance.

Patients in the most recent period were more likely to receive 200 mg/m² of melphalan as a conditioning regimen compared with 2005 to 2008 and 2001 to 2004 (90% vs 84% vs 81%, respectively). The rate of complete responses did not change substantially over the 3 time periods. “Patients [in the most recent period] tended to be more sensitive to chemotherapy, probably because they were getting more active regimens, and a higher percentage were transplanted within 6 months of diagnosis in the most recent period [42% vs 28% vs 32%],” Dispenzieri said.

Overall survival post-ASCT was significantly superior by about 15% during the most recent period compared with the earliest period (P <.001).

The early relapse rates (within 2 years) were 38%, 38%, and 35% over the 3 time periods. The only characteristic that appeared to predict early relapse was advanced disease stage. On multivariate analysis, predictors of early relapse were resistance to chemotherapy (P = .0071), International Staging System (ISS)/Durie-Salmon (DS) stage III disease at diagnosis (P = .0037), and receipt of transplant from 2001 to 2008 (P = .0179).

Use of a novel agent for post-ASCT maintenance was protective against relapse (P = .0180). There was a strong interaction between year of ASCT and type of post-ASCT maintenance on early relapse. During the 2001 the 2008 period, the hazard ratio (HR) for early relapse was 1.219 (P <.0001) compared with no maintenance or use of non-novel agents as maintenance compared with the use of novel agents. During the 2009 to 2013 period, the HR for no/other maintenance was 1.256 (P <.0001) compared with use of novel agents.

Patients who relapsed early had a 5-year overall survival rate from transplant of 32%, compared with 80% among those patients who did not have early relapse.

Among the early relapsers, post-relapse survival was significantly superior in the 2 most recent time periods compared with 2001 to 2004 (P = .006). One-year post-relapse survival was 58%, 70%, and 68% in the groups receiving ASCT during 2001 to 2004, 2005 to 2008, and 2009 to 2013, respectively. At 3 years, the post-relapse survival rates were 32%, 42%, and 41%, respectively, and at 5 years, 22%, 25%, and 23%, respectively.

In assessing post-relapse survival by when patients relapsed, patients who relapsed in the more modern era (2008 or after) had significantly superior post-relapse survival (P <.01). Comparing patients who relapsed before 2008 to those who relapsed at 2008 or later, the 1-, 2-, 3-, and 5-year post-relapse survival rates in these 2 groups were 61% and 72%, 45% and 55%, 33% and 43%, and 21% and 26%.

Multivariate analysis showed that predictors of worse post-relapse survival were early relapse (P <.0001), IgA disease (P = .0002), ISS/DS stage III at diagnosis (P <.0001), receipt of 2 or more lines of chemotherapy (P = .0048), and Karnofsky score <90% (P = .0028). Receipt of a novel agent for maintenance predicted better post-relapse survival (P <.0001).

Dispenzieri A, Kumar S, Zhang M-J, et al Trends in survival outcomes among patients relapsing early after autologous stem cell transplantation for multiple myeloma (CIBMTR Study # MM14-03). Presented at: BMT Tandem Meetings; February 23-26, 2017; Orlando, Florida. Abstract 63.

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