Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.

Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy.

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFNγ+ Spike-specific T cells. Yet the magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. We initiated an interventional phase 1 trial of a third booster shot (NCT04936997); primary outcomes were immune responses with a secondary outcome of safety. After a third immunization, the 20 participants demonstrated an increase in antibody responses, with a median 3-fold increase in virus-neutralizing titers. Yet no improvement was observed in T cell responses at 1 week after the booster immunization. There were mild adverse events, primarily injection site myalgia, with no serious adverse events after a month of follow-up. These results suggest that a third vaccination improves humoral immunity against COVID-19 in cancer patients on active chemotherapy with no severe adverse events.

Perceptions of Cancer Causes, Prevention, and Treatment Among Navajo Cancer Survivors.

Native Americans experience cancer-related health disparities. Yet, little is known about the current cancer experience in one of the largest Native American tribe, Navajo. A qualitative study of among Navajo cancer survivors, in which focus groups and individual interviews included questions related to perceptions of cancer causes, prevention, and treatment, allowed us to evaluate several aspects of the cancer experience from the Navajo perspective. An experienced, bilingual facilitator led the discussions using a standardized guide. Discussions were audio-recorded, documented by field notes, translated, as needed, and transcribed. NVivo software was used to summarize major themes according to the PEN-3 and health belief models. Navajo cancer survivors (N = 32) were both males (n = 13) and females (n = 19) that had been previously diagnosed with a variety of cancers: colorectal, breast, ovarian, cervical, esophageal, gall bladder, stomach, prostate, kidney, and hematologic. Many survivors had accurate knowledge of risk factors for cancer. Barriers to screening and clinical care included language, expense, geography, fear, lack of information, skepticism related to Western medicine, and treatment side effects. While some survivors experienced familial support, others were isolated from the family and community due to the perspective of cancer as a contagion. However, resilience, hope, trust in select community organizations, a desire to restore balance, and to support younger generations were positive attributes expressed regarding the treatment and recovery process. These evaluations need to be replicated across a larger cross-section of the Native cancer survivor community.

Physical Activity among Navajo Cancer Survivors: A Qualitative Study.

Physical activity (PA) may improve quality of life and survival among cancer survivors; however, little is known about Navajo cancer survivor PA. We evaluated Navajo cancer survivor PA habits, barriers, and preferences through focus groups and interviews (n = 32). Transcripts were coded in NVivo and major themes summarized by consensus. Survivor exercise guidelines were largely unknown, but movement, resilience and life balance were valued. Most participants reported at ≥1 mode of current PA (n = 24; 71% walking, 46% work/homesteading). Barriers to PA included treatment side effects, limited access to programs, fear of "over doing it," and family/friends encouraging rest. Preferences for PA varied.