Diffuse large B‐cell lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance

Abstract

Diffuse large B‐cell lymphoma (DLBCL) is the most common lymphoma subtype, accounting for 30–40% of lymphoma diagnoses. Although aggressive, cure is achievable in approximately 60% of cases with primary chemoimmunotherapy, and in a further substantial minority by salvage therapy and autologous stem cell transplantation. Despite promising activity in early phase clinical trials, no intensified or novel treatment regimen has improved outcomes over R‐CHOP21 in randomised studies. However, there remain several areas of controversy including the most appropriate prognostic markers, central nervous system prophylaxis and the optimal treatment for patients with high‐risk disease. This position statement presents an evidence‐based synthesis of the literature for application in Australasian practice.

Fitness criteria for Australian patients referred for chimeric antigen receptor T‐cell therapy

“…The ALA statement discusses CAR-T as an approved therapy with potential for cure but notes that 'the complexity of the procedure precludes its use in many patients, especially those with refractory lymphoma or medical comorbidities'. 1 While we do not disagree with the content of this statement, we believe that further clarifications are required. In particular, we are concerned that many practising haematologists/oncologists equate disease control and fitness criteria for CAR-T as being the same as those for ASCT.…”

“…The Australasian Lymphoma Alliance recently published a consensus practice statement (henceforth referred to as 'ALA Statement') on diffuse large B-cell lymphoma (DLBCL). 1 In this statement, a panel of experts in DLBCL made recommendations on the standard work-up and treatment of DLBCL in the Australian context including recommendations on the management of patients with relapsed/refractory (R/R) DLBCL who are not eligible for autologous stem cell transplantation (ASCT) due to comorbidities. The ALA statement notes that the management of DLBCL in transplant-ineligible patients is often non-curative, with the exception of radiotherapy in the minority of patients where all sites of disease are encompassed in a single field.…”

“…The ALA statement notes that the management of DLBCL in transplant-ineligible patients is often non-curative, with the exception of radiotherapy in the minority of patients where all sites of disease are encompassed in a single field. 1 For the majority of transplant-ineligible patients with disseminated disease, the document states that there is no standard approach, and advocates early consideration for clinical trials. 1 As the treatment site representatives for the National chimeric antigen receptor T-cell (CAR-T) Patient Prioritization Committee, a specialist group of physicians working in multi-disciplinary teams delivering CAR-T therapy in approved Australian hospitals, we note that CAR-T is an established standard of care in transplant-ineligible patients with R/R DLBCL who have failed at least two lines of therapy; [2][3][4] this indication is additional to the established indication of R/R DLBCL following prior ASCT.…”

“…1 For the majority of transplant-ineligible patients with disseminated disease, the document states that there is no standard approach, and advocates early consideration for clinical trials. 1 As the treatment site representatives for the National chimeric antigen receptor T-cell (CAR-T) Patient Prioritization Committee, a specialist group of physicians working in multi-disciplinary teams delivering CAR-T therapy in approved Australian hospitals, we note that CAR-T is an established standard of care in transplant-ineligible patients with R/R DLBCL who have failed at least two lines of therapy; [2][3][4] this indication is additional to the established indication of R/R DLBCL following prior ASCT. Two CAR-T products are publicly funded in Australia for treatment of R/R DLBCL (tisagenlecleucel and axicabtagene ciloleucel), and specialist treatment centres have been established in New South Wales, Victoria, Queensland and Western Australia accepting referrals from all states and territories.…”

Are dynamic or fixed FDG‐PET measures of disease of greater prognostic value in patients with relapsed/refractory diffuse large B‐cell lymphoma undergoing autologous haematopoietic stem cell transplantation?

“…Approximately 30%–40% of patients with diffuse large B‐cell lymphoma (DLBCL) fail to achieve durable remission after current first‐line therapy 1. Presently, salvage immunochemotherapy followed by autologous haematopoietic stem‐cell transplantation (ASCT) remains standard of care for fit patients with relapsed/refractory (R/R) DLBCL, 2–4 with long‐term cure achieved in around 40% of patients 5–7 . Recent data from CD19‐directed chimeric antigen receptor T cells (CAR‐T) challenges this paradigm, 8,9 but given the cost, complexity and toxicity of CAR‐T, ASCT is likely to remain in widespread use globally.…”