Time to plateau shows prognostic value in NDMM

This current era of novel agents has led to improved survival and increased response rates in multiple myeloma (MM) patients. Numerous studies have shown an association between a complete response (CR) from the use of novel agents and an improved overall survival (OS) in MM patients. However, 20% of transplant-eligible and transplant-ineligible MM patients who have achieved a CR will still die early (≤ 4 years). Therefore, additional prognostic factors need to be identified in order to move towards response-customized treatment.

Patrick W. Mellors, from the Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, US, and colleagues, assessed the association between survival outcomes and the time taken to reach ‘a best response plateau’ (T_Plat) in newly diagnosed MM (NDMM) patients. The findings of this study were published in the American Journal of Hematology in April 2018.

Study design:

• N = 1,099 NDMM patients (pts) diagnosed between December 2005 and December 2015 at Mayo Clinic Rochester
• Pt eligibility:
  • Initial treatment with a novel agent (IMiD, PI, or a combination)
  • Pts achieved ≤1 partial response to first-line therapy
• Time to plateau (T_Plat) was defined as time from the administration of first-line therapy to best response to first-line therapy and pts were separated into two groups:
  • Pts achieved their best response to treatment in ≤ 120 days (T_Plat ≤ 120 days)
  • Pts achieved their best response to treatment in > 120 days (T_Plat > 120 days)

Patient characteristics:

• Median age at diagnosis (years) = 63 (23–89)
• Follow-up (years) = 3.8 (0.2–11.4)
• OS (years) = 8.8 (8.1–NR)
• International Stage System (ISS): I = 220 pts; II = 327 pts and III = 230 pts
• Best response to first-line therapy: CR = 289 pts; very good partial response (VGPR) = 504 pts and partial response (PR) = 306 pts
• Cytogenetic high-risk abnormalities (del(17p), t(14;16) and t(14;20)) = 188 pts
• Most common first-line therapy: lenalidomide, and dexamethasone (Rd) = 37%; bortezomib, cyclophosphamide, and dexamethasone (VCD) = 24%; bortezomib, lenalidomide, and dexamethasone (VRd) = 16%; bortezomib and dexamethasone (Vd) = 7% and ixazomib, cyclophosphamide, and dexamethasone (ICd) = 4%

Key Findings:

• Time to plateau (months) = 4.9 (0.7–58.6)
• Duration of plateau (years) = 1.8 (0.2–11.0)
• Survival analysis showed that:
  • Pts with T_Plat > 120 days had longer median OS (mOS) and median progression free survival (mPFS) than pts with T_Plat ≤ 120 days (P < 0.001)
  • Immunomodulatory (IMiD) drugs were not associated with mOS (HR = 0.75, 95% CI, 0.53–1.06, P = 0.098)
  • Proteasome inhibitors (PIs) were not associated with mOS (HR = 0.91, 95% CI, 0.65– 1.26, P = 0.577)
  • Pts with T_Plat > 240 days demonstrated longer survival in comparison to pts with T_Plat ≤ 240 days (P < 0.001)
  • Significant improvement in mOS was maintained in patients with T_Plat > 120 days based on age (subgroups: < 65 and ≥ 65 years-old) and ASCT treatment (P < 0.001 for all comparisons)

These findings suggest a survival benefit in NDMM patients who responded more gradually to initial therapy compared to those that responded more rapidly. Time to best response (T_Plat) was also found to be an independent prognostic value for patients both eligible and non-eligible for transplant, as the effects of T_Plat remained the same after adjustments for numerous risk factors such as sex, age and best response during first-line therapy.