Two years of standard chemotherapy without hematopoietic stem cell transplant (HSCT) is the standard regimen for children, adolescents and young adults (AYAs) with low-risk first relapse of B cell acute lymphoblastic leukemia (B-ALL).¹ Low risk is defined as bone marrow with or without extramedullary (BM EM) relapse ≥36 months or isolated EM (IEM) relapse ≥18 months from initial diagnosis, and low (<0.1%) BM minimal residual disease (MRD) at the end of reinduction chemotherapy.¹ New drugs, such as blinatumomab, have been studied in this setting. Blinatumomab is a bispecific monoclonal antibody, which binds CD19 protein expressed on the surface of ALL cells and a CD3 protein expressed on T cells.¹

This is a randomized phase 3 trial with 2 arms – the control arm (block 1,2,3, all continuation and maintenance therapy with UKALLR3/mitoxantrone) compared with the experimental arm (block 1 and 2: UKALLR3/mitoxantrone, block 3: A 4-week cycle of blinatumomab, continuation as follows UKALLR3/mitoxantrone, a 4-week cycle of blinatumomab, UKALLR3/mitoxantrone, a 4-week cycle of blinatumomab, and finally maintenance with UKALLR3/mitoxantrone).¹ The primary endpoint is disease-free survival (DFS), while the secondary endpoint is overall survival (OS).¹

For BM±EM relapses, statistically significant increases in DFS and OS were seen in the blinatumomab group: The 4-year DFS was 74.0±6.4% for blinatumomab vs. 51.8±7.9% for chemotherapy (p=0.016); the 4-year OS was 96.6±2.5% for blinatumomab vs. 84.4±5.6% for chemotherapy (p=0.013)¹. Between the 2 arms, there was not a statistically significant difference in DFS or OS for IEM relapses: The 4-year DFS was 34.2±8.6% for blinatumomab vs. 39.3±8.5% for chemotherapy (p=0.73), and the 4-year OS was 81.7 7.0% for blinatumomab vs. 80.8 7.2% for chemotherapy (p=0.61).¹

A triplet combination induction therapy of lenalidomide, bortezomib and dexamethasone (RVd), followed by autologous stem cell transplantation (ASCT), and the lenalidomide (R) maintenance therapy, is the standard frontline regimen for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM).¹ Although the standard induction therapy may be efficient to a certain extent, novel strategies with higher efficacy and lesser toxicity are needed.

GRIFFIN is a randomized phase 2 study examining the efficacy and safety of daratumumab (DARA) + RVd (D-RVd) as an induction therapy, with the aim of improving the stringent complete response (sCR), minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS) in transplant-eligible NDMM patients.¹ The patients received 4 D-RVd or RVd induction cycles (21-cycles), 2 D-RVd or RVd consolidation cycles following a high-dose therapy with ASCT, and R maintenance therapy with lenalidomide (28-cycles) alone or with DARA.¹

The subgroup analysis of patients indicated that a treatment regimen integrating D-RVd during induction, consolidation and R maintenance, when combining with ASCT, was clinically effective.1 An improved depth of response was evident through sCR rates and MRD negativity rates.¹ Although results showed a certain favorability towards D-RVd, larger studies with more patients may be required to obtain conclusive data.