American Association for Cancer Research, April 8-13

The annual meeting of the American Association for Cancer Research was held this year from April 8 to 13 in New Orleans and attracted approximately 19,000 participants from around the world, including scientists, cancer survivors, clinicians, allied health professionals, and industry professionals. The conference highlighted recent advances in the treatment, management, and prevention of cancer.

In a phase 1 study, Yago Nieto, M.D., Ph.D., of the University of Texas MD Anderson Cancer Center in Houston, and colleagues found that an approach using natural killer (NK) cells complexed with a bispecific antibody is well tolerated and appears to induce a very high overall response and complete remission rate in patients with heavily pretreated CD30+ advanced lymphomas.

The authors derived the NK cells from cord blood, where the cells were then activated and complexed with a CD30/CD16A bispecific antibody. Specifically, the cord blood-derived NK cells were manufactured in the laboratory over two weeks prior to infusion, during which time they underwent preactivation with cytokines (to become more cytotoxic), expanded more than 2,700-fold, and incubated with AFM13 during one hour. Twenty-two patients received lymphodepleting chemotherapy to prevent rejection of the cord NK cells prior to their infusions of AFM13-NK cell complexes (two doses were given in an escalating approach on two different occasions, followed by three additional follow-up infusions of AFM13 alone one week, two weeks, and three weeks posttreatment with the complexed cells). The researchers found that the approach was highly active and well tolerated in the population assessed.

"We saw great safety and high activity of a novel cellular immunotherapy approach, using two cycles of the combination of AFM13 with allogeneic cord blood-derived NK cells, in patients with refractory and heavily pretreated CD30+ Hodgkin and non-Hodgkin lymphomas, who had all failed treatment with brentuximab vedotin. The donor NK cells were detectable in the serum for up to three weeks and presented an activated immunophenotype," Nieto said. "This constitutes a new, very safe and very active approach for patients with CD30+ lymphomas that have failed treatment with brentuximab vedotin."

Funding for this study was provided by Affimed Therapeutics.

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In another study, Linda Kachuri, M.P.H., Ph.D., of the University of California in San Francisco, and colleagues found that adjusting for genetic factors in the normal variation of prostate-specific antigen (PSA) levels demonstrates the potential to both reduce unnecessary negative biopsies and improve the ability to detect tumors that have a more aggressive profile.

The authors conducted the largest ever genome-wide association study (GWAS) of PSA genetics in men without prostate cancer (95,768 men). Variants across the genome that influence constitutive PSA levels were discovered. Next, the authors leveraged these findings to develop a genetic score that explains 7 to 8 percent of variation in PSA levels and applied this information to adjust observed PSA levels. The researchers demonstrated that genetically adjusted PSA is strongly associated with aggressive prostate cancer and can also be used to de-escalate potentially unnecessary invasive testing (like biopsy).

"This study is a first step for showing that genetic discoveries from GWAS can be used for improving the diagnostic performance of PSA," Kachuri said. "Rather than replacing PSA with a genetic score, we are using genetic information to make PSA measurements more informative and personalized. We hope that this accelerates the adoption of genetic scores into clinical practice."

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Philip Lupo, Ph.D., of the Baylor College of Medicine in Houston, and colleagues found that Latino children with acute lymphoblastic leukemia (ALL) who present as minimal residual disease (MRD)-negative are more likely to experience relapse compared with non-Latino White children.

The authors assembled a cohort of more than 1,600 pediatric ALL patients across seven pediatric hospitals in the Southwestern United States to evaluate factors associated with relapse. More than 60 percent of the study population self-identified as Latino. While MRD status at the end of induction was one of the strongest prognostic factors for relapse among children diagnosed with ALL, more than 50 percent of children who relapsed were MRD-negative.

"Additionally, there have been few assessments of relapse in populations where the majority of children are Latino, who also have a higher rate of ALL relapse," Lupo said. "While there is no immediate impact, it is important to understand why children who are Latino and are MRD-negative have a higher risk of relapse. This will guide strategies for improved risk stratification and treatment modifications."

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In the longest follow-up of non-small cell lung cancer (NSCLC) patients on any KRAS G12C inhibitor, Grace K. Dy, M.D., of the Roswell Park Comprehensive Cancer Center in Buffalo, New York, and colleagues found that sotorasib offers meaningful and durable efficacy as well as a safety profile consistent with earlier reports.

The researchers analyzed data on 174 patients who received sotorasib in the combined phase I and phase II studies of the trial. Most patients had received an average of two prior lines of therapy, including anti-PD-1 or anti-PD-L1 immunotherapy and platinum-based chemotherapy. The patients received the U.S. Food and Drug Administration-approved dose of sotorasib at 960 mg daily. The researchers found sotorasib to be well tolerated with prolonged tumor responses in patients with KRAS G12C-mutated NSCLC.

"Our findings demonstrate that we have a safe and effective medication available for KRAS G12C-mutated NSCLC -- confirming that we have a treatment option that is preferable to salvage chemotherapy," Dy said. "Clinical practice has already changed based on the pronounced benefit seen in our one-year analyses, with the FDA granting accelerated approval of sotorasib for these patients in May 2021. We expect that findings from the phase III CodeBreaK 200 study will further confirm the benefit we saw here."

The study was sponsored by Amgen, the manufacturer of sotorasib.

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AACR: Novel COVID-19 Vaccine Aimed at Immunocompromised Patients

THURSDAY, April 21, 2022 (HealthDay News) -- Interim results of early research show that a new vaccine against severe acute respiratory syndrome coronavirus 2, CoVac-1, induces T-cell immune responses in 93 percent of patients with B-cell deficiencies, according to a study presented at the annual meeting of the American Association for Cancer Research, held from April 8 to 13 in New Orleans.

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AACR: Adding Nivolumab to Neoadjuvant Chemo Slows Resectable NSCLC

TUESDAY, April 12, 2022 (HealthDay News) -- Neoadjuvant nivolumab plus chemotherapy results in significantly longer event-free survival and increased pathological response among patients with resectable non-small cell lung cancer compared with chemotherapy alone, according to a study published online April 11 in the New England Journal of Medicine to coincide with the annual meeting of the American Association for Cancer Research, held from April 8 to 13 in New Orleans.

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AACR: Resistance Mechanisms to CAR-T Cell Therapy ID'd in ALL

TUESDAY, April 12, 2022 (HealthDay News) -- For patients with acute lymphoblastic leukemia with resistance to C19 CAR T-cell therapy, resistance mechanisms that can be detected prior to treatment have been identified, according to a study presented at the annual meeting of the American Association for Cancer Research, held from April 8 to 13 in New Orleans.

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