Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma [Clinical trial].  

Highlights:

●      Talquetamab (anti–G protein–coupled receptor family C group 5 member D) and teclistamab (anti–B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class–exposed relapsed or refractory multiple myeloma (RRMM).

●      In this phase 1b-2 study (RedirecTT-1; NCT04586426) in patients with RRMM the incidence of grade 3 or 4 infections (which occurred in 64% of the patients) with talquetamab plus teclistamab was higher than has been observed with either therapy alone.

●      With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease).

A total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months.

Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma [Clinical trial].

Highlights:

●      In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety.

●      BV + Len + R demonstrated a statistically significant survival benefit with a manageable safety profile in heavily pretreated patients with R/R DLBCL.

ECHELON-3 (NCT04404283) is a randomized 1:1, double-blind, placebo-controlled, phase 3 trial in 230 patients comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL. With a median follow-up of 16.4 months, the median OS (primary endpoint) was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (hazard ratio, 0.63 [95% confidence interval, 0.45 to 0.89]; two-sided P=0.009).

Clearance of Driver Mutations after Transplantation for Myelofibrosis [Retrospective study].

Highlights:

●      Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear.

●      Clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival, irrespective of the underlying driver mutation.

In this study the authors used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis who were undergoing transplantation after reduced-intensity conditioning.  The two primary end points were relapse and disease-free survival.

T cell malignancies after CAR T cell therapy in the DESCAR-T registry [Retrospective study].  

Highlights:

●      The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern. The findings of this study indicate a very low risk of T cell malignancy after CAR T cell therapy.

●      Only one patient (0.03%) developed a T cell malignancy after CAR T infusion. Specifically, the patient was diagnosed with a primary cutaneous CD30+ T cell lymphoproliferative disorder 3 years after receiving tisagenlecleucel therapy for diffuse large B cell lymphoma. This was associated with the integration of a CAR clone into the tumor suppressor gene PLAAT4 (phospholipase A and acyltransferase 4). Thus, the development of this secondary T cell malignancy might be linked to the use of CAR T cell therapy.

In this study the authors analyzed 3,066 patients in the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018.

Diagnosis and management of monoclonal gammopathy of renal significance: A British Society for Haematology good practice paper [Guideline].

Key points: 

●      Patients with monoclonal gammopathy of renal significance (MGRS) may have very subtle clonal abnormalities.

●      Proteinuria ≥1.5 g/24h, hematuria and an elevated free light chain ratio (outside of the range of 0.27–1.65 in patients with an eGFR >60 mL/min per 1.73 m²) increased the likelihood of finding MGRS. The recommendation (2C) is that a kidney biopsy should be highly considered in such patients.

●      Cases should always be discussed within the context of a multidisciplinary team, as the final histological classification of some entities will depend on the clinical picture and serological findings (2C). See Table 1: Histological findings in MGRS-specific diagnoses. 

●      All patients who have a potential MGRS lesion on renal biopsy who would benefit from treatment of the underlying clone should have a full haematological work-up, including bone marrow aspiration and biopsy with flow cytometry (1B). 

●      Imaging should be considered for patients with a detectable B-cell clone (CT scan neck/thorax/abdomen/pelvis) or plasma cell clone (whole body MRI or PET-CT scan) (1C).

●      The aim of disease-specific treatment should be to achieve the deepest clonal response possible; autologous stem cell transplant should be considered in patients who would be potentially listed for renal transplantation who are not in a complete response (2C).