Case 4: CAR T-Cell Therapy for Heavily Pretreated Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDC. Ola Landgren, MD, PhD:In this presentation, we will spend time talking about one of the newer therapies, CAR [chimeric antigen receptor] T-cell therapy, for heavily pretreated patients with multiple myeloma.

The patient that I would like to present is a 57-year-old gentleman. He was diagnosed 24 months prior to this event. At that time, he had stage III multiple myeloma. A cytogenetic profile indicated that he was intermediate risk. He was initially treated with RVd [lenalidomide/bortezomib/dexamethasone] therapy and had achieved a VGPR [very good partial response]. After the combination therapy regimen, he underwent high-dose melphalan with autologous stem cell transplant.

His laboratory findings indicate a hemoglobin level of 11.4 g/dL and a creatinine clearance of 1.0 mg/dL. The M spike had gone up from 0.6 g/dL to 1.2 g/dL and, subsequently, to 1.5 g/dL. The patient reported feeling tired but continued to function quite well despite these facts. He was started on therapy with carfilzomib, lenalidomide, and dexamethasone. After 6 cycles of therapy, he achieved a partial response.

He was subsequently hospitalized because of a pneumonia event and complained of increasing back pain, fatigue, and weakness. Lab work was done again, showing an M spike of 2.1 g/dL and a beta₂microglobulin level elevated at 6.2 mg/L. His albumin level was quite low—at 2.1 g/dL—and he had a very low creatinine clearance—32 mL/min. He was now started on daratumumab with pomalidomide and dexamethasone. He achieved stable disease after 3 months on this treatment regimen.

In August 2018, imaging was conducted with a PET/CT [positron emission tomography/computed tomography] scan showing FDG [fluorodeoxyglucose] uptake revealing destruction. So these are osteolytic lesions. A bone marrow biopsy was conducted, showing 70% plasma cell infiltration and abnormal-appearing plasma cells, confirming CD138-positive light chain—restricted plasma cells. His ECOG status was determined to be 2.

Let’s spend a few minutes talking about one of the new CAR T-cell therapy protocols. This is the bb2121 study that was recently presented at the ASCO [American Society of Clinical Oncology] Annual Meeting in Chicago—anti-BCMA [B-cell maturation antigen] CAR T-cell therapy in patients with relapsed/refractory multiple myeloma. This is an update from the multicenter phase I trial.

As I pointed out, it’s for patients with relapsed/refractory myeloma. This ASCO presentation was an update focusing on safety and efficacy, appropriately. Forty-three patients were included in this analysis. Patients had received 3 or more prior lines of therapy, including a PI [proteasome inhibitor] and an IMiD [immunomodulatory imide drug], or they could be double refractory. For the purpose of the phase I trial, the requirement was 50% or more BCMA expression on the plasma cells. Patients received 1 infusion of bb2121 following lymphodepletion with fludarabine and cyclophosphamide, given for a total of 3 days.

Here are some of the safety data. As you can see on this slide, the total CRS [cytokine release syndrome] rate was as high as 63%. Focusing on grade 3 or higher events, it was 5%. Neurotoxicity was 33%; and, for grade 3 and higher, the rate was 2%. The classical hematologic manifestations for adverse events are also illustrated by this slide. The bb2121 safety was manageable at doses up to 800 x 10⁶of CAR T cells.

Most of the CRS events were grade 1 and 2. Tocilizumab and steroids were used infrequently—21% and 9%, respectively. There were 2 grade 3 CRS events. Importantly, these were seen within 24 hours. There was 1 grade 4 neurotoxicity event, and that was reversible. There were no additional events during the expansion phase.

So let’s take a look at the responses for the evaluable patients from this presentation. If you start looking at the patients who received 50 million cells, and that’s the left column, the overall response rate was 33%. For patients who received 150 million cells, it was 57%. Patients who received more than 150 million cells had a 95.5% overall response rate. The complete response rates were 0%, 43%, and 50%, respectively. If you look at the median duration of response, it was 1.9 months, to not estimated, to 10.8 months.

Transcript edited for clarity.