Four Baseline Characteristics Predict CR/sCR in Multiple Myeloma

Investigators have identified immunoglobulin G (IgG) heavy chain, soluble B-cell maturation agent (sBCMA), prothrombin time and international normalized ratio (PR-INR), and high vector copy number in drug product as predictors for response in patients with multiple myeloma, according to an analysis of data from the KarMMa trial (NCT03361748).¹

Nina Shah, MD

In a poster presented at the 2022 Transplantation & Cellular Therapy Meetings, investigators led by Nina Shah, MD, a clinical professor of medicine and hematologist specializing in the treatment of multiple myeloma at University of California San Francisco Health, concluded that PR-INR (OR, 0.005; P = .0365), IgG, and sBCMA were negative predictors for complete response (CR) or stringent CR (sCR). Vector copy number in drug product was a positive predictor (OR, 1.486; P = .0168).

In the phase 2 KarMMa trial, idecabtagene vicleucel (ide-cel) treatment induced deep responses in patients with relapsed/refractory multiple myeloma. Of the 140 patients in the trial, 26% of patients achieved minimal residual disease (MRD)–negative status and 79% of patients who achieved a CR or better were MRD negative.²

The median progression-free survival (PFS) was 8.8 months (95% CI, 5.6-11.6) overall; among patients with a CR or better, the median PFS was 20.2 months (95% CI, 12.3-NE). Overall survival (OS) data were immature, but the median OS was 19.4 months (95% CI, 18.2-NE) and the 12-month OS rate was 78%.

Eligible patients received at least 3 prior treatment regimens for multiple myeloma including an immunomodulatory drug, a PI, and an anti-CD38 antibody, and were refractory to their last treatment regimen. Patients received one of 3 doses of ide-cel (150 x 10⁶, 300 × 10⁶, or 450 × 10⁶ CAR-positive T cells) following lymphodepletion with 30 mg/m2 daily fludarabine and 300 mg/m2 daily cyclophosphamide.

A total of 128 patients received ide-cel infusion, 1 of whom discontinued after unsuccessful management of the CAR T-cell product.

The median patient age was 61 years (range, 33-78) and patients had a median of 6 years (range, 1-18) since their diagnosis. A majority of the patients were male (59%), had high tumor burden (51%), BCMA expression ≥50% at screening (85%), ECOG performance status of 1 (53%), and Revised International Staging System disease stage of II (70%). Thirty-five percent of patients had high-risk features.

In this analysis, 42 of 128 (32.8%) patients achieved CR/sCR. Eighty-six (67.1%) patients had non-CR/sCR responses.

Shah et al said that baseline characteristics were generally balanced between CR/sCR and non-CR/sCR group.

According to multivariate analysis, sBCMA level was lower in patients who had CR/sCR compared with those who did not (191 ng/mL vs 340 ng/mL; OR, 0.646; P = .0007). Baseline sBCMA level of 300 ng/mL or less was the threshold separating those with CR/sCR from those with other responses.

“As sBCMA is an indicator of tumor burden and can affect therapies targeting BCMA, selecting for patients with lower tumor burden and controlling tumor burden during manufacturing or bridging therapy may be important in achieving CR/sCR with ide-cel,” investigators wrote.

Investigators further assessed sBCMA levels in 112 patients who received bridging therapy—37 patients had CR/sCR while 75 had non-CR/sCR responses following ide-cel treatment. In patients who did not receive bridging therapy, those who did not have CR/sCR saw greater sBCMA increases from screening to baseline. Further, baseline sBCMA levels were lower among those with CR/sCR whether or not they received bridging therapy.

The absence of IgG heavy chain disease also correlated with CR/sCR. Only 18% of patients with IgG heavy chain disease had CR/sCR compared with a 57% CR/sCR rate in those with other type or undetected heavy chain. Furthermore, the median PFS favored those who did not have IgG heavy chain disease (8.1 vs 11.9 months).

Investigators also identified ferritin, D-dimer, and sodium levels as correlates of response in univariate analysis. They said this finding suggests that improved patient health characteristics and lower inflammation could impact outcomes.

“The correlates identified in this analysis are generally consistent with those previously reported with CD19-directed CAR T cell therapies and may help clinicians to decide which patients have the best chance of a deep clinical response to ide-cel in real-world practice,” Shah et al wrote.

References

1. Shah N, Munshi N, Berdeja JG, et al. Baseline correlates of complete response to idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy in patients with relapsed and refractory multiple myeloma (RRMM): subanalysis of the KarMMa trial. Presented at: the 2022 Transplantation & Cellular Therapy Meetings; Salt Lake City, UT; April 23-26, 2022. Abstract 223.
2. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850