General MM

Response outcomes in patients with newly diagnosed multiple myeloma

Survival rates for patients with multiple myeloma (MM) have improved over recent years due to the development of targeted therapies, stem cell transplantation, and combination approaches.1 Response to first-line treatment is one of the most important prognostic factors associated with survival in patients with newly diagnosed MM (NDMM).2 The relationship between depth of response and survival has previously been established, however, the impact of time to response on outcomes remains unclear.3

Dr. Nidhi Tandon, from the Division of Hematology, Mayo Clinic, Rochester, US, and colleagues, published findings from a retrospective analysis evaluating the prognostic impact of response time in the front-line therapy setting in 2705 consecutive patients with NDMM, within 90 days of diagnosis.4 Response data after two and four cycles of front-line therapy, and overall best response were assessed in 840 patients. The primary end-point was defined as patients who achieved a very good partial response (VGPR).

Key findings:
  • Median follow-up from start of first-line treatment: 71 months (95% CI, 67–79)
  • Response rate of ≥ VGPR:
  • Following two cycles of therapy: 29% (240/840)
  • Following four cycles of therapy: 42% (350/840)
  • As best overall response: 66% (552/840)
  • Early responders (≥ VGPR after 2 cycles) observed to have higher rates of:
    • Light-chain only disease: 44% vs 20%, P < 0.001
    • Anemia: 36% vs 28%, P = 0.04
    • Renal insufficiency: 21% vs 9%, P < 0.001
    • Hypercalcemia: 10% vs 5%, P = 0.03
    • High-risk cytogenetics: 28% vs 19%, P = 0.03
    • International Staging System (ISS) stage III disease: 39% vs 27%, P = 0.002
    • Patients receiving a triplet regimen in first-line treatment: 62% vs 41%, P < 0.001
    • Patients receiving a proteasome inhibitor-based regimen in first-line treatment: 66% vs 36%, P < 0.001
    • Patients receiving autologous stem cell transplant (ASCT) in first-line treatment: 52% vs 41%, P < 0.001
  • No significant difference in progression-free survival (PFS) or overall survival (OS) seen between patients achieving a response of ≥ VGPR or < VGPR following 2 or 4 cycles of therapy
  • Overall best response of ≥ VGPR was associated with significantly higher PFS compared to patients achieving < VGPR response: 33 months vs 22 months, P < 0.001
  • Overall best response of ≥ VGPR was associated with significantly higher median OS compared to < VGPR response: 102 months vs 77 months, P = 0.003

In the multivariate analysis, patients were stratified by transplant status to examine the impact of response on survival following adjustment for treatment received.

  • In the transplant group, inferior PFS was only predictive by high-risk cytogenetics: HR = 1.7 (95% CI, 1.1–2.6), P = 0.03
  • In the non-transplant group, inferior PFS had two predictive features: high risk cytogenetics (HR = 1.6; 95% CI, 1.2–2.3; P = 0.006) and the presence of renal impairment (HR = 2.3; 95% CI, 1.4–3.9; P = 0.002)
  • Patients achieving an early response did not improve PFS: transplant group (HR = 1.1; 95% CI, 0.7–1.6; P = 0.8) and non-transplant group (HR = 1.2; 95% CI, 0.8–1.7; P = 0.4)
  • In the transplant group, inferior OS was predicted by high-risk cytogenetics (HR = 1.2 [95% CI, 1.1–4.4], P = 0.04) and ISS stage III disease (HR = 2.1 [95% CI, 1.02–4.2], P = 0.007)
  • In the non-transplant group, adverse prognostic factors include high-risk cytogenetics (HR = 2.1 [95% CI, 1.4–3.2], P < 0.001) and age (HR = 7.0 [95% CI, 2.1–23.8], P = 0.002)
  • Patients achieving an early response did not improve OS: transplant group (HR = 1.6; 95% CI, 0.9–2.9; P = 0.1) and non-transplant group (HR = 1.5; 95% CI, 1.0–2.4; P = 0.07)

The authors concluded that the results from this retrospective analysis illustrate the achievement of a deep response following first-line treatment, independent of the time to response, is prognostic for improved long-term outcomes in patients with NDMM.

References
  1. Kumar S.K. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1; 111(5): 2516–2520. DOI: https://doi.org/10.1182/blood-2007-10-116129
  2. Kyle R.A. & Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009 Jan; 23(1): 3–9. DOI: 10.1038/leu.2008.291 [Epub 2008 Oct 30]
  3. Schaar C.G. et al. Early response to therapy and survival in multiple myeloma. Br J Haematol. 2004 Mar 08; 125(2): 162–166. DOI: https://doi.org/10.1111/j.1365-2141.2004.04884.x
  4. Tandon N. et al. Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma. Blood Adv. 2019 Mar 12; 3(5): 744–750. DOI: 10.1182/bloodadvances.2018022806
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