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May 31, 2020 - 08:05 pm Posted in ASCO and ASH Posted in ASCO Conference Coverage Posted in Breast Posted in Lymphoma (includes NHL, HL, CNS Lymphoma) Posted in Melanoma (includes BCC) Posted in Multiple Myeloma comments0 Comments

Sunday’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting featured late-breaking data from a phase 3 trial evaluating early local therapy in metastatic breast cancer and the results of the phase 3 ENDURANCE trial.

Other important studies from the meeting were the ALPHA trial, which is evaluating an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy, and the C-144-01 trial, which is evaluating an autologous tumor infiltrating lymphocyte (TIL) therapy.

Early local therapy offers no survival benefit in patients with de novo metastatic breast cancer and an intact primary tumor, according to the results of a phase 3 trial by the ECOG-ACRIN Research Group (Abstract LBA2).

The trial included 256 patients who received optimal systemic therapy before being randomly assigned to either continue optimal systemic therapy (n=131) or receive optimal systemic therapy with locoregional therapy (n=125).

The 3-year overall survival (OS) rate was not different for the locoregional therapy arm compared with the optimal systemic therapy alone arm (68.4% vs 67.9%; P=0.63) and neither was the risk of death (HR=1.09; 90% CI, 0.80 – 1.49).

Although the locoregional therapy arm had a reduced risk of locoregional recurrences/progression compared with the optimal systemic therapy alone arm (HR=0.37; 95% CI, 0.19 – 0.73), no improvements were seen for health-related quality of life (HRQOL). At one timepoint (18 months), HRQOL was significantly worse for the locoregional therapy arm (P=0.001).

“For de novo stage metastatic breast cancer, existing data supports that locoregional therapy does not improve survival and should not be routinely applied in this population,” said study discussant Julia White, MD, professor of radiation oncology at The Ohio State University.

Carfilzomib and Bortezomib Tie for First

The replacement of carfilzomib for bortezomib in a regimen of bortezomib, lenalidomide, and dexamethasone (VRd) did not improve outcomes for patients with newly diagnosed multiple myeloma, results showed in the second interim analysis of the phase 3 ENDURANCE trial (Abstract LBA3).

Patients who received carfilzomib, lenalidomide, and dexamethasone (KRd; n=545) had a similar progression-free survival (PFS; HR=1.04; 95% CI, 0.8 – 1.3; P=0.74) and OS (HR=0.98; 95% CI, 0.71 – 1.36; P=0.92) to those who received VRd (n=542). A higher proportion of particularly good partial responses was seen with KRd compared with VRd (55.5% vs 49.9%).

KRd had a significantly higher rate of cardiac, pulmonary, and renal treatment-related adverse events (16.1% vs 4.8%; P<0.001), while VRd had a significantly higher rate of peripheral neuropathy (53.4% vs 24.4%; P<0.001). No difference in frequency of secondary primary cancers was seen.

Study discussant Jesus Berdeja, MD, director of myeloma research at Sarah Cannon Research Institute, pointed out that KRd costs nearly $16,000 more per cycle than VRd, which totals to a nearly $100,000-difference for 12 cycles.

“In newly diagnosed multiple myeloma without high-risk features, VRd and KRd appear to be equivalent options for frontline treatment,” Dr Berdeja said. “Comorbidities and toxicity profiles should guide the choice between the two regimens in any individual patient.”

ALPHA Trial Debuts Off-the-Shelf CAR T

An off-the-self allogeneic CAR T-cell therapy known as ALLO-501 appeared safe and showed clinical activity in a small group of patients with relapsed or refractory large B-cell or follicular lymphoma, according to data from the single-arm phase 1 ALPHA trial (Abstract 8002).

“Allogeneic CAR T-cell therapy may provide the benefits of autologous CAR T-cell therapy, while also addressing its challenges,” said study presenter Sattva Neelapu, MD, MD Anderson Cancer Center. “It has the potential to treat all eligible patients, the convenience of repeat dosing, and simplifies the logistics of manufacturing.”

Patients received CD19-targeted ALLO-501 at one of three dose levels and, during lymphodepleting chemotherapy, an investigational monoclonal antibody called ALLO-647, which targets CD52. Patients were heavily pretreated (median of 4 prior therapies), and 4 patients previously received autologous CAR T-cell therapy.

About one-third of patients (7 of 22) had cytokine release syndrome, which included only one grade 3 event and no grade 4. Half of patients developed infection, most of which was grade 1 (23%) or 2 (18%). There were no reports of graft-versus-host disease.

At a median follow-up of 3.8 months, 12 of 19 patients (63%) available for efficacy analysis achieved a response, which included 7 complete responses (37%). Nine patients who achieved a response continue to have a response.

Dr. Neelapu said these results suggest that the safety and the short-term efficacy, in terms of the response rates, for this product is “comparable” to autologous CAR-T products that are currently in clinic. “Further follow-up is necessary to determine the durability of those responses.”

C-144-01 Trial Shows Potential of TILs

Autologous TIL therapy lifileucel appeared safe and to have clinical activity in patients with unresectable metastatic melanoma, according to the results of cohort 2 from the phase 2 C-144-01 trial (Abstract 10006).

Lifileucel is an autologous adoptive cell transfer therapy that involves surgically resecting a patient’s tumor and sending it to the manufacturing facility. Tumor infiltrating lymphocytes (TILs) are then obtained from the tumor, expanded, shipped back to clinical sites, and infused into the patient. Patients in cohort 2 (n=66) received lifileucel that was cryopreserved before shipment. Patients also received up to 6 doses of interleukin-2 after infusion to promote expansion of the TILs.

Most patients (97.0%) had grade 3 or 4 treatment-emergent adverse events, with thrombocytopenia (81.8%), anemia (56.1%), febrile neutropenia (54.5%), and neutropenia (39.4%) being the most common. The number of adverse events decreased over time.

Overall, 24 (36.4%) patients achieved a response, which included 2 complete and 22 partial responses. The disease control rate was 80.3%. At a median follow-up of 18.7 months, the median duration of response had not yet been reached (range, 2.2 – 26.9+ months). Responses were seen across subgroups, which include age, PD-L1 status, and BRAF mutation status.

“Notable, observed responses tended to deepen over time,” said study presenter Amod Sarnaik, MD, Moffitt Cancer Center. “These data therefore demonstrate potential efficacy and durability of response in a patient population with severely limited treatment options.”

By Christina Bennett, MS

 

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