ASH 2019 Day 3 – CAR T-Cell Therapy, LCAR-B38M and SMM Treatment Session

DAY 3 – Morning Session 1 

Monday morning at ASH proved to be a busy time for myeloma presentations as there were two simultaneous sessions! In the first session of the day, we learned more about chimeric antigen receptor (CAR) T-cell therapy—3 new constructs and the long-term follow-up results from a trial of construct we’ve reported on last year—LCAR-B38M. Also presented were a couple of studies on the treatment of patients with smoldering multiple myeloma (SMM).

CAR T-cell Therapy

Making some news already is a new CAR T-cell construct called JNJ-4528 which targets the common protein on myeloma cells—B-cell maturation antigen (BCMA). JNJ-4528 is engineered to latch onto BCMA on two different areas of the protein designed to make this CAR T-cell therapy hold on to myeloma cells tighter. This construct is identical to LCAR-B38M—which is also being reported on as described below. Dr. Deepu Madduri of the Icahn School of Medicine at Mount Sinai reported the results of a trial named CARTITUDE-1 that used JNJ-4528 for the first time in patients with relapsed/refractory myeloma: (ABSTRACT 577 https://ash.confex.com/ash/2019/webprogram/Paper121731.html).

  • 29 patients who had previously received up to 5 therapies (many of whom were refractory to proteasome inhibitors, immunomodulatory drugs, and Darzalex) were treated with JNJ-4528.
  • All patients responded to the treatment, and—of those patients who could be assessed—all patients achieved minimal residual disease (MRD) negativity.
  • The majority of patients experienced the common side effects of this type of therapy namely cytokine release syndrome (CSR), low white blood cells, low red blood cells, and low platelets.
  • The investigators concluded that JNJ-4528 treatment results in early and deep responses with a manageable safety profile and these results are consistent with what has been observed with the existing LCAR-B38M construct previously reported.

Investigators from Xi’an, China  provided their long-term follow-up data on the safety and efficacy of the LCAR-B38M CAR T-cell therapy (ABSTRACT 579 https://ash.confex.com/ash/2019/webprogram/Paper124953.html).  Their initial results of 74 patients treated showed encouraging efficacy and manageable safety. In their update presented today, they reviewed the outcome of 57 of those original patients who had received the LCAR-B38M therapy.

  • The overall response rate was 88% and the majority of responders achieved MRD negativity.
  • The median duration of response was 22 months and 27 months for those patients who were MRD negative.
  • The median time before disease progression was 20 months for all responding patients and 28 months for MRD-negative patients.

Another study from China reported on yet another BCMA-targeted CAR T-cell therapy that is considered “fully human” named CT103A (ABSTRACT 582 https://ash.confex.com/ash/2019/webprogram/Paper128468.html). The investigators treated 16 patients with relapsed/refractory myeloma (many of whom had previously received up to 3 treatments (and also 4 patients who had previously received a different CAR T-cell therapy) and all patients responded to CT103A therapy within 2 weeks. All patients developed CRS.

BCMA is not the only target for CAR T-cell therapy constructs. CD19—another protein on the surface of myeloma cells—is also a target. Investigators from China studied a sequential CAR T-cell treatment plan. First, they administered CD19-targeted CAR T-cells to patients followed by the administration of BCMA-targeted CAR T-cells. Chinese investigators reported their results of the sequential infusion of these 2 types of CAR T-cells in patients with relapsed/refractory myeloma (ABSTRACT 578 https://ash.confex.com/ash/2019/webprogram/Paper129740.html). Twenty-eight patients were treated and all patients were resistant to proteasome inhibitors and immunomodulatory drugs. Eighty-six percent of patients responded to sequential treatment and all experienced CRS.

Smoldering Multiple Myeloma (SMM)

For patients with SMM, a study presented by Dr. Mark Bustoros at the Dana-Farber Cancer Institute investigated the use of Ninlaro + Revlimid + dexamethasone (IRd) for patients who are considered to be at highest risk of progression to active myeloma (ABSTRACT 580 https://ash.confex.com/ash/2019/webprogram/Paper128519.html). In this trial, 53 high-risk SMM patients—defined as having the following laboratory measurements: M spike: >2g/dL; free light change ratio: >20; and bone marrow plasma cells: >20% —were treated with the triplet combination.  Overall, 94% of patients responded to treatment.The most common severe side effects were high blood pressure, low phosphate levels, rash, low platelets, low white blood cells, and high blood sugar levels—but these were observed in very few patients.

Another study of patients with SMM investigated the process by which to measure the extent of minimal residual disease in patients following treatment using a blood test rather than a bone marrow sample. Investigators from Spain used a blood test call the Quantitative Immunoprecipitation Mass Spectrometry (QIP-MS) which can detect M protein. This test was used to test the blood of 90 SMM patients (at high risk of progression to active myeloma) following treatment with Kyprolis-Revlimid-dexamethasone followed by autologous stem cell transplant (ASCT) and compared to other traditional tests (ABSTRACT 581 https://ash.confex.com/ash/2019/webprogram/Paper127717.html).  M-protein monitoring by QIP-MS was more sensitive than electrophoresis methods and looked to be equivalent to MRD assessment by other standard procedures used like next-generation flow cytometry.  More studies are expected to determine the future role of QIP-MS testing for SMM patients. And, the investigators noted that in patients who achieve a complete response, QIP-MS could serve as a gateway for MRD testing by providing doctors the appropriate time to perform another bone marrow biopsy.