Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma

B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis

“…The baseline characteristics of the included studies are listed in Table 1. A total of 314 patients were included in the 18 studies, [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] all of which were single-arm early phase studies that included only patients with RRMM (17 studies) or newly diagnosed myeloma (1 study). Patients included in RRMM studies were heavily pretreated and received a median of 6 prior lines of treatment (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, 1-2 autologous stem cell transplants).…”

BAFF inhibition in SLE—Is tolerance restored?

“…While APRILdeficient mice have normal immune development, class switching to IgA and maintenance of serum IgA levels is highly APRIL-dependent. Specifically, anti-BAFF-R 16 and anti-BCMA 17 CARs are being developed for the treatment of B cell leukemia/lymphoma and multiple myeloma, respectively, while APRILexpressing CARs target TACI and BCMA expressing cells. 24 F I G U R E 1 BAFF, APRIL, and their receptors and splice variants: Both BAFF and APRIL multimerize: BAFF multimerizes into 60-mers via its flap region whereas APRIL multimerizes on cells surfaces by binding to proteoglycans.…”

Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma

“…The disappearance of the paraprotein is affected not only by cessation of its production by the malignant clone – the phenomena we are really trying to appraise – but also by its clearance from serum, a physiological phenomenon that is relatively fast for free light chain, but that takes several weeks for IgG and IgA. This may be crucial for the evaluation of novel therapies such as chimeric antigen receptor (CAR)‐T cells that can lead to fast and profound suppression, if not the elimination of the malignant clone (Raje et al , ). As currently instituted, the simple detection of non‐quantifiable paraprotein by immunofixation only in serum is sufficient to downgrade to very good partial response (VGPR) a response that would otherwise be CR.…”

“…Given that the current partial response (PR) and VGPR categories have little difference in long term outcomes and patients with CR with disease burden >10 −4 have similar outcomes to VGPR patients (Lahuerta et al , ), perhaps a more sensible future approach to response assessment would limit classification based on protein detection to the boundaries of the current VGPR category, and utilize NGS or NGF solely to determine any deeper level of remission (Fig ). Such an approach would be more practical, less influenced by the lagging of paraprotein clearance and better able to stratify patients in an era when a higher proportion of patients achieve CR during initial therapy (Attal et al , ; Facon et al , ) or even during management of relapsed disease (Dimopoulos et al , ; Palumbo et al , ; Chari et al , ; Raje et al , ).…”

“…Responses, as measured by standard criteria (Kumar et al , ), are cumulative and often influenced by the lagging clearance of the paraprotein from serum. A treatment that leads to the rapid elimination of near all MM cells in a short period of time, may not produce a short‐term complete remission due to the persistence of small amounts of paraprotein in serum (as seen with CAR‐T cells) (Raje et al , ). Patients are often already in sCR/CR when they arrive at ASCT and an additional reduction of MM burden cannot be appreciated using standard response assessment.…”