ASH 2023 to Highlight Options in Care for Blood Diseases—for Those Who Have Access

The 65th American Society of Hematology (ASH) Annual Meeting and Exposition, which takes place this weekend in San Diego, California, will showcase the growing number of treatment choices in blood cancers and disorders—along with the nagging question: who gets to receive them?

Findings that compare chimeric antigen receptor (CAR) T-cell therapy with bispecific antibodies, that show the long-term benefit of Bruton tyrosine kinase (BTK) inhibitors, and that offer hope in sickle cell disease (SCD) will share the limelight with data that show gaps in outcomes based on a patient’s insurance status and inexplicable differences in out-of-pocket costs to Medicare patients for life-saving drugs.

Attendees will gather against the backdrop of the November 28, 2023, FDA announcement that regulators are looking into reports of T-cell malignancies among a small number of patients treated with CAR T-cell therapy.

Which Way to Treat?

Tuesday’s late-breaking session, Sunday’s plenary session, and other science will highlight comparisons of treatment options:

• The late-breaking PERSEUS trial, a phase 3 randomized study that compares a quadruple therapy—daratumumab (Darzalex) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd)—with VRd alone in patients with newly diagnosed multiple myeloma who can receive an autologous stem cell transplant.
• Another late-breaking study involving ibrutinib (Imbruvica) and venetoclax (Venclexta), SYMPATICO, examines the combination in a phase 3 trial for patients with mantle cell lymphoma (MCL). Also, on Monday the phase 2 BOVen study will examine the use of zanubrutinib (Brukinsa), obinutuzumab (Gazyva), and venetoclax (Venclexta) in high-risk MCL patients.
• Sunday’s plenary session will feature results from the phase 3 IsKia trial, which examines use of isatuximab (Sarclisa) with carfilzomib (Krypolis), lenalidomide, and dexamethasone (KRd) vs KRd alone as pretransplant induction and posttransplant consolidation in patients with multiple myeloma.
• The phase 3 TRANSFORM-1 study will compare navitoclax with ruxolitinib (Jakafi) vs ruxolitinib alone in patients with untreated myelofribrosis.

For all the talk of whether to use a bispecific antibody or CAR T-cell therapy in large B-cell lymphoma, direct comparisons are hard to come by. An indirect comparison will be presented late Saturday with an abstract that uses trial data to compare efficacy of subcutaneous epcoritamab (Epkinly), a bispecific T-cell engager, with the CAR T-cell therapy tisagenlecleucel (Kymriah).

Options and Sequencing in CLL/SLL

Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute | Image credit: DFCI

Multiple studies will report on options available to patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). On Saturday, Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute will offer follow-up data from the ALPINE trial at 36 months. ALPINE, last year’s show-stopper, previously showed the BTK inhibitor zanubrutinib offered 35% better progression-free survival and improved safety over ibrutinib after 25 months for these patients, especially those at high risk. In an interview with The American Journal of Managed Care^®, Brown discussed the unanswered questions from last year’s presentation that she will cover.

“I think many people felt that the 2-year follow-up was still just a little bit short in terms of what we've seen with CLL,” she said, noting the comparison with the ELEVATE-RR study that examined acalabrutinib vs ibrutinib and had a 36-month follow-up.

“People have been very eager to see whether the benefit of zanubrutinib holds up at this year's follow-up,” Brown said.

There’s no shortage of other science involving CLL, including new data from the phase 3 FLAIR study involving the use of minimal residual disease (MRD) testing to direct the use of ibrutinib plus venetoclax compared with fludarabine, cyclophosphamide, and rituximab (FCR).

Brown called this study “thought provoking” as investigators “take the approach of determining how long it takes an individual to get to undetectable MRD, and then they double the treatment duration. So, each person gets a duration of treatment based on how long it takes them to get on technical MRD—and that might be several years—3, 4, even up to 6 years in this trial,” which she noted is considerably longer than most venetoclax trials have reported.

“There's going to be a lot of discussion and debate around those results after we see exactly what they are on Sunday,” Brown said.

Finally, Brown noted she will be presenting data regarding pirtobrutinib, a noncovalent BTK inhibitor now being examined in patients who had previously received a covalent BTK inhibitor. Investigators are still learning about sequencing these therapies, she said.

New Therapies and Rare Diseases

Once again, ASH will spotlight recent advances in SCD, including Saturday’s special session on SCD disease centers as well as a highlighted study on patients who have received lovotibeglogene autotemcel (lovo-cel) gene therapy for 5 years. Abstracts involving care for patients with SCD will be highlighted at ASH’s second Guidelines Champions session.

Tuesday’s late-breaking session will also feature results for the phase 2 AUGMENT-101 study involving revumenib, which is being evaluated in patients with relapsed/refractory KMT2Ar acute leukemia. This therapy would address an area of unmet need, as patients with this acute leukemia currently relapse after conventional chemotherapy and hematopoietic stem cell transplant. In October, officials with Syndax announced the trial for this first-in-class Menin inhibitor had been stopped early because the primary end point had been reached.

Cost and Access to Care

ASH features abstracts and sessions highlighting the high cost of the novel therapies that can bring remission for blood cancers and disorders, as well as the health equity issues that result when a patient’s type of insurance or lack of insurance keeps some from gaining access to these treatments. Notable abstracts assess the lifetime cost of care for patients with CLL, being presented Saturday by Farrukh T. Awan, MD, of University of Texas Southwestern in Dallas; and examine differences in the price of imatinib (Gleevec) among different Medicare Part D plans, which can result in disparities in out-of-pocket costs for beneficiaries, being presented Sunday by Myung Sun Kim, MD, of Compass Oncology.

Authors from City of Hope, centered in Duarte, California, will present findings on Monday regarding the effects of a patient’s type of health coverage on access to autologous stem cell transplantation with the effects on racial inequity in overall survival among patients with multiple myeloma. This disease disproportionately affects patients of color.