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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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  1. Home
  3. Deeper Response Predicts Better Outcomes In High-risk-smoldering-myeloma: Results Of The I-prism Phase Ii Clinical Trial.
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  3. Deeper Response Predicts Better Outcomes In High-risk-smoldering-myeloma: Results Of The I-prism Phase Ii Clinical Trial.

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Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical

Omar Nadeem1,2, Michelle P Aranha3,4,5, Robert Redd6

  • 1Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. omar_nadeem@dfci.harvard.edu.

Nature Communications
|January 3, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Early treatment for high-risk smoldering multiple myeloma (HR-SMM) with ixazomib, lenalidomide, and dexamethasone shows promise. Deep responses, like complete response and MRD negativity, significantly improve progression-free survival, indicating better long-term outcomes.

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Area of Science:

  • Hematology
  • Clinical Oncology
  • Translational Research

Background:

  • Early intervention in high-risk smoldering multiple myeloma (HR-SMM) is beneficial, but predictors of long-term outcomes remain unclear.
  • No prior studies have evaluated if biochemical progression or response depth influences long-term results in HR-SMM patients receiving early therapy.

Purpose of the Study:

  • To assess the predictive value of biochemical progression and response depth on long-term outcomes in HR-SMM patients treated with ixazomib, lenalidomide, and dexamethasone.
  • To evaluate the efficacy and safety of the combination therapy in HR-SMM.

Main Methods:

  • A single-arm, phase II clinical trial (I-PRISM) involving 55 HR-SMM patients treated with ixazomib, lenalidomide, and dexamethasone.
  • Progression-free survival (PFS), biochemical PFS, overall response rate (ORR), complete response (CR), very good partial response (VGPR), minimal residual disease (MRD) negativity, and single-cell RNA sequencing were assessed.

Main Results:

  • The median PFS was not reached (NR), with a median follow-up of 50 months. Biochemical PFS was 48.6 months.
  • An overall response rate (ORR) of 93% was observed, with 31% achieving CR and 45% achieving VGPR or better. CR correlated with the absence of SLiM-CRAB criteria and biochemical progression.
  • MRD negativity predicted 100% 5-year biochemical PFS versus 40% in MRD-positive patients (p=0.051). Tumor MHC class I expression and a lower proportion of GZMB+ T cells within CD8+ T cells were linked to proteasome inhibitor response and suboptimal outcomes, respectively.

Conclusions:

  • Deep responses, including CR and MRD negativity, are crucial for achieving durable remissions and favorable long-term outcomes in HR-SMM patients treated with ixazomib, lenalidomide, and dexamethasone.
  • Biochemical progression and response depth are significant predictors of long-term outcomes in HR-SMM.
  • Exploratory analyses suggest potential biomarkers for treatment response and prognosis, warranting further investigation.