Day 0 – Symposium Day at ASH2017

Friday, December 8, 2017

December 8th is actually the day before ASH officially begins, often called “Symposium” day.

However, my first session was last night’s Bone Marrow Transplant Clinical Trials Network Multiple Myeloma (BMTCTN MM) Intergroup meeting, a group focused supporting myeloma clinical trials involving transplants.

There were probably 100 physicians attending the BMTCTN meeting led by Drs. Phillip McCarthy and Saad Usmani, and several gave 10–15 minute presentations on minimal residual disease (MRD) testing used within the transplant setting. Currently, everyone agrees that MRD is good as a prognostic tool. That is, MRD-negative (MRD-) implies longer progression-free survival (PFS) and overall survival (OS) to a lesser extent (because trials haven’t been going on that long). One of the goals of MRD research is to be able to use it as a surrogate marker for clinical trial, instead of waiting for OS results. In addition, MRD can perhaps guide treatment.

Some takeaways from this meeting:

  • Last year, the STAMINA trial compared stem cell transplant (SCT) compared to SCT + consolidation, and compared to tandem (SCT). In all of these scenarios, the initial treatment is followed by maintenance. The results showed that there was essentially no progression-free survival or overall survival differences amongst the three arms. And yet, now looking at MRD pre-SCT, pre-maintenance, and one-year post-maintenance did show MRD- differences for arm 1 (42%, 77%, 78%); arm 2 (40%, 76%, 85%); and arm 3 (47%, 83%, 92%). So, I wondered, does that mean the study—which originally reported after 3 years—did it not study for a long enough time period?
  • Doing imaging (PET-CT) should probably be done in conjunction with MRD testing since the location of the bone marrow sample used for MRD can make a difference.
  • Dr. Amirita Krishna described her future DRAMMATIC study S1804 that incorporates Response-Guided-Therapy for MRD- patients.
  • Dr. Nikhil Munshi described the i²TEAM Initiative, an international retrospective study that will use 7 large trials, n=4500 patients to evaluate differences between MRD+ and MRD- results, with the goal of establishing MRD as a surrogate endpoint.
  • Dr. Manisha Bhutani discussed immune profiling. He described a subset of patients whose multiple myeloma clones, wishing a given patient had different mutations (e.g. BRAF, KRAS, and others) depending on the location of their different MM tumors. She referred to this as “spatial heterogeneity.” Wow, what a complex disease.

Today, I attended the IMF Symposium “Getting Clear Answers to Complex Treatment Challenges in Multiple Myeloma: Case Discussions.” I estimate about 1000 people attended and watched Dr. Brian G.M. Durie moderate a panel of myeloma experts. Panelists included Drs. S. Vincent Rajkumar, Philippe Moreau, Bruno Paiva, and Jesús San Miguel.

The format is quite interesting:

  1. A patient case is presented.
  2. Multiple-choice questions are presented about one of the five topics.
  3. The audience votes on their answers, and the results are displayed.
  4. Next, a presenter describes the best treatment practices and reasons for these practices.
  5. All presenters vote on the multiple-choice question.
  6. Finally, the audience votes again. (Have minds been changed?)

The doctors provided their insights on topics:

  • Dr. Bruno Paiva spoke on Accurately Diagnosing MM: When Should Systemic Myeloma Treatment Be Initiated?
  • Dr. S. Vincent Rajkumar spoke on Individualized Approaches to Treatment Selection forInduction Therapy
  • Dr. Philippe Moreau addressed Transplant, Consolidation, and Maintenance: The Role of MRD in Monitoring
  • Dr. Jesús San Miguel discussed Therapeutic Strategies After First Relapse Following Initial Therapy
  • Dr. Brian G.M. Durie talked about Current and Future Options in Patients with Late Relapse

Some interesting conclusions:

  • Dr. Paiva stated that progression to multiple myeloma from high-risk smoldering multiple myeloma (HRSMM) patients is 25% per year for the first two years. For standard risk SMM, it’s 5% per year. Dr. S. Vincent Rajkumar commented, “For HRSMM patients, there seems to be a choice between aggressive (curative?) treatment and non-aggressive treatment. We don’t know which is best so treat within clinical trials.”
  • Dr. S. Vincent Rajkumar presented preferred induction for the following cases:
  1.  Standard risk, 62yo: Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone (RVd)
  2.  Standard risk, 75yo: RVd or RVd-Lite
  3. High-risk, del 17p: Kyprolis (carfilzomib), Revlimid (lenalidomide) and dexamethasone (KRd) for younger patients; RVd for older patients
  4. For renal-compromised patients, Cytoxan (cyclophosphamide), Veclade (bortezomib),and dexamethasone, or CyBorD, should be chosen over Revlimid.
  • Dr. Moreau considered the questions of consolidation, single autologous stem cell transplant compared to tandem autologous stem cell transplants, as well as how to improve and how to monitor treatment results.
  • All doctors believe that SCT and maintenance should be done. However, consolidation doesn’t have a consensus of opinion. And perhaps, trials testing newer induction therapies (e.g. Velcade, Revlimid and dexamethasone with or without daratumumab; or Kyprolis, Revlimid, and dexamethasone with or without daratumumab) will make a difference.
  • And, there was near unanimous consensus that PET-CT scans should be used as a diagnostic tool at baseline and before maintenance. When the question, “If a patient is MRD- three years past maintenance, is the patient cured?” was asked, the MM panels all said “not sure” or “no.” They commented that some patients may be cured and others not.
  • Dr. San Miguel reminded folks that treatments at first relapse could be the following three choices:
  1. Kyprolis, Revlimid, and dexamethasone (KRd). The ASPIRE trial showed 8 months OS improvement over Rd.
  2. Revlimid, Cytoxan, and dexamethasone (a Dutch trial will show 72% Overall Response Rate (ORR).
  3. Daratumumab combinations.
  • Dr. Brian G.M. Durie focused on late relapse patients who should consider daratumumab, pomalidomide, and dexamethasone; pomalidomide, cyclophosphamide, and dexamethasone, or CAR T cells that are engineered to attack the b-cell maturation antigens (BCMAs) on myeloma cells (although results are not enough to assess this fully yet) as well as monoclonal antibodies (mAB) used to attack BCMAs. These last two therapies will be presented by Glaxo-Smith-Kline during this year’s ASH.

So, bad weather in Atlanta has already thrown a wrench into some presentations, and we’ll be missing some more tomorrow. Fortunately, the morning sessions will be recorded and available to ASH badge holders. I’ll continue to blog about the meetings I attend.

So…“Baby, it’s cold out there!”

Wishing you the best of health!