ASH 2019 Day 3 – Newly Diagnosed Myeloma & Relapse Predictors Session

DAY 3 – Morning Session 2 

The second morning session today focused on newly diagnosed myeloma and various combination strategies, as well as predictors of relapse.

Currently, Revlimid (lenalidomide) is the only drug approved by the FDA as maintenance therapy for myeloma patients after autologous stem cell transplantation (ASCT) due to its ability to prolong disease progression. Several trials at the ASH Meeting explored combinations other agents with Revlimid and/or replacing it with an alternative for patients who do not tolerate Revlimid.

Dr. Ravi Vij from Washington University in St Louis—and Multiple Myeloma Research Consortium (MMRC) site investigator—studied the use of Ninlaro as part of a maintenance therapy and directly compared Revlimid to Ninlaro (ABSTRACT 602 https://ash.confex.com/ash/2019/webprogram/Paper130644.html). In his phase 2 trial, which was conducted in conjunction with other MMRC sites, myeloma patients with newly diagnosed myeloma who underwent ASCT were treated with consolidation therapy (additional cycles of therapy—prior to the use of maintenance therapy—following a stem cell transplant to help deepen responses) consisting of the triplet combination of Ninlaro-Revlimid-dexamethasone (IRd). Following consolidation therapy, patients were treated with maintenance therapy—either Ninlaro or Revlimid.

  • At the time of his presentation, 215 patients had completed IRd consolidation therapy and 191 received maintenance therapy—90 patients received Ninlaro and 94 received Revlimid.
  • More patients experienced side effects affecting blood cell counts on Revlimid maintenance than Ninlaro maintenance.
  • More patients required dose reductions or discontinued because of side effects due to Revlimid maintenance than Ninlaro maintenance
  • More patients discontinued treatment due to disease progression on Ninlaro maintenance than Revlimid maintenance

Another combination regimen being studied as induction, consolidation, and maintenance therapy for patients with newly diagnosed myeloma who are candidates for ASCT is Empliciti-Revlimid-dexamethasone (ERd). Dr. Jesus Berdeja from the Sarah Cannon Research Institute presented results of a phase 2 trial investigating this triplet regimen (ABSTRACT 603 https://ash.confex.com/ash/2019/webprogram/Paper130277.html).

  • Fifty-two patients were treated and 84% had responded to ERd treatment.
  • The most common side effects were fatigue, diarrhea, and nausea. Neuropathy was seen in about one-third of patients, and all events were relatively mild.
  • The study investigators concluded that despite a high response rate for all patients, the high-risk patients did not benefit as much as standard risk patients with respect to the length of time before disease progressed. ERd will continue to be evaluated as a treatment for standard-risk patients.

With currently available treatments, many myeloma patients respond to treatment and many more can achieve minimal residual disease (MRD) negativity—which is associated with a longer time until disease progresses. However, some patients may not respond to therapy and some that quickly relapse following treatment. Investigators from Italy analyzed data from a clinical trial to see if they could identify the main factors that could predict which patients may relapse quickly (ABSTRACT 605 https://ash.confex.com/ash/2019/webprogram/Paper125588.html).

They analyzed data obtained from 474 newly diagnosed patients who had enrolled on the FORTE trial (Kyprolis-Revlimid-dexamethasone as induction followed by ASCT or consolidation with the same triplet regimen and then followed by maintenance with Revlimid or Revlimid + Kyprolis).

  • The study found creatinine levels, bone marrow plasma cells and the presence of deletion of chromosome 17 reduced the probability of achieving MRD negativity.
  • Patients at high risk of early relapse included those with R-ISS II/III, high lactate dehydrogenase (LDH) levels (as used in R-ISS staging), and high bone marrow plasma cells.
  • Ultimately, the achievement of MRD negativity is the factor that may reduce the risk of early relapse.

The last study of the session focused on the monoclonal antibody Xgeva (denosumab)—a treatment that is used to reduce bone-related disorders in myeloma patients like bone fractures and is similar in its outcomes to the bisphosphonate zoledronic acid, according to the trial that led to its FDA approval. A more recent phase 3 study comparing Xgeva to zoledronic acid showed that Xgeva showed a clinically meaningful benefit by prolonging time until disease progression especially for patients who intended to go on to receive an autologous stem cell transplant. The study presented by Dr. Evangelos Terpos of Greece and headed by Dr. Noopur Raje of the Massachusetts General Hospital investigated whether Xgeva or zoledronic acid could prolong the time until disease progression in patients who intend to go on to receive an autologous stem cell transplant (ABSTRACT 606 https://ash.confex.com/ash/2019/webprogram/Paper127290.html).  Indeed, in the intent to undergo ASCT group, Xgeva prolonged the time until disease progression by 10 more months than zoledronic acid.