2018 ASH – Upfront Stem Cell Transplant update

Morning 9:30 AM-11:00 AM

Clinical Autologous Transplantation: Results: Multiple Myeloma: Upfront Autologous Transplantation

The Saturday morning myeloma sessions kicked off with a discussion of high-dose chemotherapy and stem cell transplantation for patients with newly diagnosed myeloma. These talks focused on the use of different drugs either prior to or after receiving a transplant to deepen responses rates (that is, helping a patient achieve a very good partial response or better or even achieving minimal residual disease negativity—in which no myeloma cells can be detected, by sensitive assays, in the bone marrow). One of these talks highlighted data from a clinical trial from our Multiple Myeloma Research Consortium (MMRC). Another talk focused on whether patients at risk of an early relapse (within 12 months of undergoing a stem cell transplant) could be identified. And another addressed whether a single or double stem cell transplant was associated with better outcomes.

Proteasome inhibitors, like Velcade, have been shown to be useful for patients with newly diagnosed myeloma, particularly those who go on to receive a stem cell transplant. Clinicians from Italy, looked at the effectiveness of a “second-generation” proteasome inhibitor—Kyprolis—in these types of patients (ABSTRACT 121 https://ash.confex.com/ash/2018/webprogram/Paper112093.html). Dr. Francesca Gay and her colleagues at the European Myeloma Network, conducted a trial (call the Forte trial) using three different combinations of Kyprolis before and after transplant:

  1. 158 patients received Kyprolis + Revlimid + dexamethasone—KRD (as induction and consolidation following stem cell transplantation);
  2. 159 patients received  Kyprolis + cyclophosphamide + dexamethasone—KCD  (as induction and consolidation following stem cell transplantation; and
  3. 157 patients received Kyprolis + Revlimid + dexamethasone—KRD—alone (with no consolidation and no stem cell transplantation).

The results of the trial showed that more patients receiving either of the 2 KRD combinations (with or without the stem cell transplant) achieved very good partial responses or better and minimal disease negativity (that is, undetectable myeloma cells in the bone marrow) than those who received the KCD combination (with transplant). Our own CoMMpass data also show that KRD may be a reasonable combination for newly diagnosed patients—the data will be presented on Monday, December 3 (ABSTRACT 799 https://ash.confex.com/ash/2018/webprogram/Paper112289.html). If KRD with and without transplant provides similar outcomes to patients, these results call in to question whether patients benefit in the long term with the combination regimen KRD without needing a transplant.

Clinicians from the United Kingdom wanted to determine whether they could identify patients who are at risk of a relapse following a stem cell transplant. Dr. Ceri Bygrave led an investigation (ABSTRACT 122 https://ash.confex.com/ash/2018/webprogram/Paper111117.html) of patients on the Myeloma XI trial who had undergone a stem cell transplant and looked at the characteristics of patients who relapsed within 12 months of the transplant (178 patients) compared to those who relapsed after 12 months (1,096 patients).  When looking at these 2 groups of patients, she noted that achieving a very good partial response or better or receiving maintenance therapy did not prevent an early relapse (relapse within 12 months). The main clinical characteristics of patients who experienced an early relapse compared to those who relapsed after 12 months were:

  • Lower  average hemoglobin values
  • Lambda light chain subtype
  • Higher average plasma cell percentage
  • ISS stage 3 disease
  • Two or more high-risk genetic markers

Dr. Bygrave noted that it is necessary to identify high-risk patients at the time of diagnosis since the long-term outcome is poor for patients who relapse within 12 months of a stem cell transplant and there are no standard treatment approaches. Dedicated trials for these patients are needed.

The next abstract is the first of several abstracts to be presented that highlight the clinical studies led by the Multiple Myeloma Research Consortium (MMRC). This particular MMRC study—headed by Dr. Ravi Vij at Washington University in St. Louis—looked at the role of consolidation therapy (additional cycles of therapy—prior to the use of maintenance therapy—following a stem cell transplant to help deepen responses) to determine whether long-term outcomes (such as lengthening the time before myeloma progresses). The consolidation therapy that was investigated (ABSTRACT 123 https://ash.confex.com/ash/2018/webprogram/Paper109920.html) was the combination of Ninlaro + Revlimid + dexamethasone (IRD). This combination of drugs is noteworthy because all are administered orally. On this trial, 172 patients with newly diagnosed myeloma received some form of induction therapy followed by a stem cell transplant. Within 4 months of the transplant, patients received 4 cycles of the IRD consolidation therapy. The results that Dr. Vij reported include:

  • Minimal residual disease negativity rates improved from 26% after transplant to 37% after IRD consolidation (these results were mirrored using a more sensitive measurement assay: 19% to 27%)
  • Response rates also improved from 76% prior to IRD consolidation to 85% after consolidation

This consolidation regimen provides a convenient and simplified treatment for patients following a stem cell transplant. Right now, Ninlaro is only approved for patients with relapsed myeloma.

Stay tuned for further updates tomorrow!