ASCO 2022 Meeting Report — Hematologic Malignancies

The 2022 American Society of Clinical Oncology (ASCO) annual meeting, held in Chicago June 3–7, highlighted important advances in hematologic cancer research. Here, Associate Editor Dr. Michael E. Williams reviews key trials. Meeting abstracts can be viewed in the ASCO meeting library.

The phase 3, multicenter, industry-funded SHINE trial tested the addition of the Bruton tyrosine kinase inhibitor ibrutinib to standard chemoimmunotherapy in older adults with previously untreated mantle cell lymphoma (abstract LBA7502). A total of 523 patients aged 65 and older who were not candidates for autologous stem-cell transplantation consolidation were randomized to receive either oral ibrutinib (560 mg) or placebo once daily. All patients also received bendamustine (90 mg/m²) and rituximab (375 mg/m²) every 4 weeks for six cycles. Patients with a complete or partial response continued receiving ibrutinib or placebo daily until progressive disease or unacceptable toxicity, plus rituximab maintenance once every 8 weeks for up to 12 additional doses.

At a median follow-up of 85 months, 44% of patients in the ibrutinib group had disease progression or died, compared with 58% of placebo recipients (hazard ratio, 0.75; P=0.01). Median progression-free survival (PFS) was over 2 years longer in the ibrutinib group. There was no difference in overall survival (OS). The incidences of pneumonia and atrial fibrillation were higher in ibrutinib recipients; no unexpected toxicities were observed.

These results confirm a PFS benefit but not an OS benefit for the addition of ibrutinib to bendamustine-rituximab in first-line treatment of mantle cell lymphoma. Notable findings include the early separation of PFS curves by 6 months after completion of bendamustine-rituximab, consistent with delayed progression and relapse with maintenance ibrutinib plus rituximab versus rituximab alone.

Read more about the study in the New England Journal of Medicine (N Engl J Med 2022; 386:2482).

To assess the role of autologous stem-cell transplantation (ASCT) and long-term lenalidomide maintenance in the era of highly active triplet induction therapy, investigators conducted the phase 3, multicenter DETERMINATION trial (abstract LBA4). A total of 722 patients aged 65 or younger with newly diagnosed symptomatic myeloma received an induction cycle of lenalidomide, bortezomib, and dexamethasone (RVD) and were then randomized to receive either RVD alone (7 additional cycles) or RVD (4 additional cycles) plus high-dose melphalan and ASCT consolidation. Both groups received daily lenalidomide as maintenance therapy until disease progression or unacceptable side effects.

Median duration of maintenance therapy was 36.4 months in the RVD-alone group and 41.5 months in the transplantation group. At a median follow-up of 76 months, median PFS (primary outcome) was 46 months in the RVD-alone group versus 68 months in the transplantation group. The estimated 5-year OS was roughly 80% in both arms; of note, 28% of 278 patients in the RVD-alone arm subsequently had ASCT.

Grade 3 or higher treatment-related adverse events, primarily hematologic, were more common among transplantation recipients (94% vs. 78% for RVD alone). The cumulative 5-year rates of secondary cancers (10%) did not differ between the arms.

These results confirm a significant benefit for ASCT consolidation following RVD induction to provide durable PFS. Undetectable measurable residual disease (MRD) was achieved in a higher percentage of patients in the ASCT arm; this study arm also showed a trend toward improved 5-year OS among patients with high-risk cytogenetic profiles. The higher PFS in this study than in a prior multicenter RVD trial that used only 1 year of lenalidomide maintenance therapy suggests a benefit for long-term maintenance lenalidomide in both study arms.

Read more about the study in the New England Journal of Medicine (N Engl J Med 2022; 387:132).

Transplant-eligible patients with high-risk acute myeloid leukemia (AML) who achieve complete remission following induction chemotherapy undergo consolidative allogeneic stem-cell transplantation (allo SCT). To assess the impact of pretransplant MRD, investigators conducted the multicenter retrospective Pre-MEASURE study (abstract 7006), which used banked remission blood samples collected within 100 days before allo SCT for ultra-deep next-generation DNA sequencing of mutated FLT3, NPM1, IDH1, IDH2, and KIT to detect MRD.

The analysis included 448 patients aged 18 or older who had one or more of the above gene mutations at the time of diagnosis, underwent first allo SCT between 2013 and 2017, and had sufficient DNA sample and clinical data available. Detection of a pretransplant mutant allele frequency ≥0.01% for FLT3-ITD, NPM1, or both was associated with a 67% relapse probability and 3-year relapse-free survival of only 19%. Persistent IDH1 or IDH2 mutations were not associated with relapse.

This precision medicine approach identifies patients at high risk of AML relapse after allo SCT who may benefit from alternative pretransplant consolidation, targeted therapeutic agents, or conditioning regimens.

The ECHELON-1 trial compared standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) to A+AVD, in which brentuximab vedotin was substituted for bleomycin, as initial therapy in patients with stage III or IV classic Hodgkin lymphoma. The previously reported primary analysis showed a significant modified PFS benefit for A+AVD but no difference in OS (NEJM JW Oncol Hematol Mar 2018 and N Engl J Med 2018; 378:331).

Investigators now report that the preplanned 6-year analysis in the intent-to-treat population (N=1334) showed a significant OS benefit for A+AVD versus ABVD (hazard ratio, 0.590; 95% CI, 0.40–0.88; P=0.009). Estimated 6-year OS rates were 93.9% versus 89.4%, with PFS estimates of 82.3% vs. 74.5%, respectively.

Overall, A+AVD had a comparable long-term safety profile to ABVD, aside from increased peripheral neuropathy related to brentuximab vedotin, which improved or resolved in most patients during follow-up. Patients on the A+AVD regimen required cytokine support for neutropenia and increased risk of infections; fewer patients in the A+AVD arm required second-line therapy or stem-cell transplantation, and rates of second primary cancers were lower than in the ABVD arm.

These findings further establish A+AVD as a preferred frontline regimen for newly diagnosed advanced stage Hodgkin lymphoma. A+AVD has been selected as the standard of care control arm for the ongoing multicenter U.S. Intergroup phase 3 trial comparing nivolumab plus AVD versus A+AVD in patients ≥12 years of age (SWOG Intergroup S1826; NCT03907488).

Read more about the study in the New England Journal of Medicine (N Engl J Med 2022; 387:132).