Schapira, Lidia

AbstractBackgroundBreast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling.MethodsIn the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0‐III BC who reported ≥1 postdiagnosis live birth were sent an investigator‐developed survey.ResultsOf 119 eligible women, 94 (79%) completed the survey. Median age at diagnosis was 32 years (range, 17–40) and at first postdiagnosis delivery was 38 years (range, 29–47). Most had stage I or II (77%) and HR+ (78%) BC; 51% were nulligravida at diagnosis. After BC treatment, most (62%) conceived naturally, though 38% used assisted reproductive technology, 74% of whom first attempted natural conception for a median of 9 months (range, 2–48). Among women with a known inherited pathogenic variant (n = 20), two underwent preimplantation genetic testing. Of 59 women on endocrine therapy before pregnancy, 26% did not resume treatment. Hypertensive disorders of pregnancy (20%) was the most common obstetrical condition. Nine percent of newborns required neonatal intensive care unit admission and 9% had low birth weight.ConclusionAmong women with live births after BC treatment, most conceived naturally and having a history of BC did not appear to negatively impact pregnancy complications, though the high rate of hypertensive disorders of pregnancy warrants further investigation. The prolonged period of attempting natural conception for some survivors suggests the potential need for improved understanding and counseling surrounding family planning goals after BC.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

PURPOSE Erb-B2 receptor tyrosine kinase 2 ( ERBB2)–positive breast cancer (BC) is particularly common in young women. Genomic features of ERBB2-positive tumors before and after chemotherapy and trastuzumab (chemo + H) have not been described in young women and are important for guiding study of therapeutic resistance in this population. METHODS From a large prospective cohort of women age 40 years or younger with BC, we identified patients with ERBB2-positive BC and tumor tissue available before and after chemo + H. Whole-exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. RESULTS Twenty-two women had successful WES on samples from at least one time point; 12 of these had paired sequencing results from before and after chemo + H and 10 had successful sequencing from either time point. TP53 was the only significantly recurrently mutated gene in both pre- and post-treatment samples. MYC gene amplification was observed in four post-treatment tumors. Seven of 12 patients with paired samples showed acquired and/or clonally enriched alterations in cancer-related genes. One patient had an increased clonality putative activating mutation in ERBB2. Another patient acquired a clonal hotspot mutation in TP53. Other genomic changes acquired in post-treatment specimens included alterations in NOTCH2, STIL, PIK3CA, and GATA3. There was no significant change in median ERBB2 CN (20.3 v 22.6; Wilcoxon P = .79) between paired samples. CONCLUSION ERBB2-positive BCs in young women displayed substantial genomic evolution after treatment with chemo + H. Approximately half of patients with paired samples demonstrated acquired and/or clonally enriched genomic changes in cancer genes. ERBB2 CN changes were uncommon. We identified several genes warranting exploration as potential mechanisms of resistance to therapy in this population.

10503 Background: Prior data suggests that the risk of second primary breast cancer (SPBC) is higher among women diagnosed with primary breast cancer (BC) before age 40. There is evidence that risk differs by primary tumor characteristics, cancer treatments, and genetic predisposition. However, studies investigating risk of SPBC by clinical risk factors are often limited by low numbers of young women and lack of complete patient data, particularly regarding germline genetic risk. Methods: Using the Young Women’s BC Study (YWS), a prospective cohort of 1,302 women ≤40 years diagnosed with BC from 2006-2016, we sought to compare clinical and treatment characteristics among women who developed an SPBC vs. those who did not. The analytic cohort included women diagnosed with Stage 0-III BC who did not undergo bilateral mastectomy (N = 685). Demographics, genetic testing and results, clinical events, and treatment data were collected through self-report on baseline and follow-up surveys (every 6 months for 3 years, then annually). Detailed tumor and treatment information, confirmation of genetic testing results, and new and recurrent cancer events were obtained through regular and triggered medical record review. Univariate and multivariate Cox proportional hazards models were used to examine associations of age, race, genetic testing results, hormone receptor status, stage, and grade of primary tumor, and cancer treatments with SPBC. Participants were censored at the time of local recurrence, metastasis, death, or loss of follow-up. Results: At a median follow-up time of 9.9 years [inter-quartile range (IQR) = 6.6-12.0 y], 17 patients developed an SPBC (2.5%), in whom 3 occurred in the ipsilateral breast after lumpectomy as primary BC surgery. Median time from primary BC diagnosis to SPBC diagnosis was 4.2 years (IQR = 3.3-5.6 y). Compared to those who did not develop an SPBC, a greater percentage of women who developed an SPBC had in situ disease as their primary BC (24% v. 6%) and were of Ashkenazi descent (12% v. 5%). In the 577 women who had had genetic testing, 544 (94%) were non-carriers of pathogenic variants. Risk of SPBC was 2.2% (N = 12) in non-carriers and 9.1% (N = 3) in the 33 carriers. In Cox univariate analyses, carriers had a 4.1 times higher risk of SPBC compared to non-carriers (HR = 4.14, 95% confidence interval (CI) = 1.67-14.66, p = 0.03), and primary diagnosis with in situ BC was associated with a 5-fold increased risk of SPBC (HR = 5.02, 95% CI = 1.63-15.41, p = 0.005). Both factors remained strongly associated with SPBC when tested together in a multivariate model. Conclusions: This prospective study demonstrated a low risk of SPBC in the first 10 years after diagnosis of early BC in young women who are not germline pathogenic variant carriers. The finding that risk of SPBC was higher after in situ primary BC at a young age warrants further investigation. These findings have important implications for the treatment and follow-up care of young women with BC.

505 Background: Increased TILs are associated with better prognosis in triple-negative BC, including in patients (pts) age < 40. However, the role of TILs remains unclear in HR+/HER2- BC and little data exist in young pts, in whom immune microenvironment could be altered by age-related host/tumor differences. We assessed the extent and composition of immune infiltration in HR+ tumors of young women and correlated with clinicopathologic features and survival outcomes. Methods: From a prospective cohort study of women with BC diagnosed age ≤40, we identified those with stage I-III HR+/HER2- BC and available pre-treatment (tx) tumor tissue. Multiplexed immunofluorescence was used to quantify cytotoxic T (CD8+), T helper (Th, CD3+CD8-), T regulatory (Tregs, FOXP3+CD3+) and exhausted T (PD1+CD8+) cells in stroma and tumor. Univariate analyses tested associations between clinicopathologic variables and immune markers by high or low expression, divided based on median. High vs. low TILs were evaluated in Cox regression analyses for invasive breast cancer-free survival (iBCFS), distant disease-free survival (DDFS) and overall survival (OS). Results: In 390 pts, median age was 37 years (21-40), most had grade 2 (51%), T1 (65%), N0 (63%) tumors and 67% received adjuvant chemotherapy. Black pts (n = 17) had higher expression of stromal CD8+ ( P= .010), FOXP3+CD3+ ( P= .027) and PD1+CD8+ TILs ( P= .043); intratumoral TILs did not differ by race. Older age (36-40) was associated with high expression of CD8+ ( P= .033) and PD1+CD8+ TILs ( P= .031) within stroma and CD3+CD8- TILs within tumor ( P= .046). Grade 3 tumors had higher stromal and intratumoral expression of CD3+CD8- ( P= .002; P< .001) and FOXP3+CD3+ TILs ( P= .020; P< .001). No differences in TILs were seen according to recency of pregnancy, BRCA1/2 status or T/N stage. Over a median follow up of 8 years, 85 iBCFS events, 64 DDFS events and 37 deaths occurred. High stromal expression of CD3+CD8- TILs was associated with better iBCFS (HR 0.49, P= .002) and DDFS (HR 0.57, P= .046), which remained significant when adjusted for T/N stage, grade and chemotherapy (iBCFS HR 0.41, P< .001; DDFS HR 0.45, P= .008). High stromal expression of CD3+CD8- and FOXP3+CD3+ TILs was associated with better OS (HR 0.47, P= .038) and iBCFS (HR 0.58, P= .018), respectively, on adjusted analyses only. High intratumoral expression of CD3+CD8- and FOXP3+CD3+ TILs was associated with better iBCFS (HR 0.59, P= .025; HR 0.63, P= .043) after adjustment only. Conclusions: The distribution of TIL subtypes in young women’s HR+ BC varied according to race, age and grade. High stromal and intratumoral expression of Th and Tregs was associated with improved BC outcomes. Characterization of immune cell subsets could help refine the prognostic value of TILs in HR+ BC, particularly in young pts who may benefit from individualized escalated/de-escalated tx strategies.

Abstract Background: Breast cancer (BC) is the most common malignancy among women of reproductive age. Given limited data describing the conception and pregnancy experience of young BC survivors, we sought to explore these outcomes to inform counseling of women interested in future childbearing. Methods: Participants with stage 0-III BC in the Young Women’s Breast Cancer Study (NCT01468246), a multi-center, prospective cohort of women diagnosed at age ≤ 40 from 2006-2016 who reported ≥ 1 live birth from a pregnancy after diagnosis were sent a survey with investigator-developed questions focused on their first post-diagnosis live birth. Women who had been diagnosed with BC during pregnancy were excluded from this analysis. The survey assessed conception, use of assisted reproductive technology (ART), pre-implantation genetic testing (PGT), endocrine therapy (ET), and peripartum complications. Summary statistics are presented. Results: 92/119 eligible women completed the survey (response rate: 77%). Median age at diagnosis was 32 (range:17-40) years and at delivery was 37 (range: 29-47) years. Median time from diagnosis to delivery was 58 months (range: 11-154). Most women had stage 2 BC (43%, 40/92); 68% received chemotherapy (63/92); about half (51%, 47/92) were nulligravida at diagnosis. Overall, 61% of pregnancies were conceived naturally (56/92) and 39% with ART (36/92): 32% by in-vitro fertilization (IVF, 29/92), 7% with fertility medications only (6/92), and 1 with intrauterine insemination. 38% of IVF pregnancies were conceived using products from fertility preservation prior to BC treatment (11/29). Among women who used ART, 74% attempted to conceive naturally (25/36) for a median of 9 (range: 2-48) months prior to pursuing ART. The most common reasons for pursuing ART include infertility following BC treatment (33%, 12/36) and expediting conception to resume treatment (17%, 6/36). 11% of those with known inherited pathologic variant mutations underwent PGT (2/19). Reasons for not pursuing PGT included belief in more effective cancer risk reduction in the future (29%, 5/17), not being offered PGT (24%, 4/17), high cost (12%, 2/17), no interest in IVF (12%, 2/17), acceptable odds for inheriting the mutation (24%, 4/17), and belief in other risk reduction strategies (18%, 3/17); 1 woman reported ethical concerns. Of 57 women who took ET pre-pregnancy (63%), nearly all (96%, 55/57) discontinued ET &gt; 3 months prior to attempting to conceive; 1 discontinued after awareness of pregnancy. Of those who had received prior ET, 60% resumed ET (34/57) a median of 3 (range: 1-50) months after pregnancy. Among 23 women who did not resume, 13 (23%) had completed the recommended duration; the remaining 10 reported one or more of the following reasons: felt better while off (28%, 6/23), desire for another child (22%, 5/23), and desire to breastfeed (17%, 4/23). Median time to delivery was 39 (range: 28-42) weeks with 12% delivering preterm &lt; 37 weeks (11/92). 47% had a Caesarean section (43/92), with prolonged labor the most common indication (33%, 14/43). Hypertensive disorders of pregnancy (HDP, 20%, 18/92), gestational diabetes (7%, 6/92), small for gestational age (7%, 6/92), and postpartum hemorrhage (5%, 5/92) were the most common obstetrical complications. 9% of women had newborns requiring NICU admission (8/92) and 9% had low birth weight (8/92). Conclusion: Among young BC survivors with a live birth following diagnosis, most conceived naturally, with the majority who used ART first attempting natural conception. There was limited use of PGT among mutation carriers with ¼ not having been offered testing. Patient reported peripartum complications appear consistent with population norms, though the relatively higher rate of HDP bears further research. Among those yet to complete their ET, a notable proportion did not resume following delivery. This novel data may help to inform the care of young breast cancer survivors pursuing pregnancy. Citation Format: Kimia Sorouri, Tal Sella, Shoshana Rosenberg, Margaret Loucks, Kathryn Ruddy, Shari I. Gelber, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Ann Partridge. Conception and Pregnancy Among Young Breast Cancer Survivors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-05.

Abstract Background: Breast cancer (BC) is the most common malignancy in women of reproductive age, and the incidence of the disease is rising in this population. Many of these women are interested in childbearing after their BC treatment and a substantial minority will go on to have a live birth. Some will also want to breastfeed. However, there is only limited information available regarding the experience of young BC survivors breastfeeding following treatment. Methods: Participants in the Young Women’s Breast Cancer Study (YWS), a multi-center, prospective cohort study of women diagnosed with BC at age ≤ 40 years between 2006-2016, who reported at least one live birth following their diagnosis with stage 0-III BC were sent an additional survey including investigator-developed questions focused on breastfeeding after breast cancer treatment. Women who had been diagnosed with BC during pregnancy were excluded from this analysis. The survey assessed whether they breastfed, reasons for attempting and stopping breastfeeding, breastfeeding with the treated breast and untreated breast, and supports. Summary statistics, including medians and proportions, are presented. Results: Of 118 eligible women sent a survey, 92 completed the survey (78% response rate). Median age at diagnosis of BC was 32 (range: 17-40) years and at delivery was 37 (range: 29-47) years. 54% of women had attempted to breastfeed (50/92). Among those who had not, 93% noted a history of bilateral mastectomies (39/42). Additional reasons for not attempting to breastfeed included no interest regardless of BC history (5%, 2/42) and 1 woman underwent a unilateral mastectomy and did not think her supply would be sufficient. Among the women who did attempt breastfeeding, 68% had undergone lumpectomy and radiotherapy (34/50) with 85% of those women reporting that the treated breast did not produce milk (29/34). The 5 women who produced milk from the treated breast noted that the supply was substantially less than the untreated breast. To assist with breastfeeding, 76% used a pump only on the untreated breast (38/50) and 14% on both breasts (7/50). Women breastfed for a median of 5.5 (range:&lt; 1-60) months and 64% were “somewhat”/“very much” satisfied with their ability to breastfeed (32/50). The most common reasons cited for stopping breastfeeding included having completed the planned duration (36%, 18/50), to start/resume endocrine therapy (22%, 11/50), and to resume breast imaging (8%, 4/50). Among patients who had not undergone a double mastectomy, 47% recalled receiving specific information about breastfeeding after a history of breast cancer (25/53), most commonly from the oncology team (56%, 14/25), lactation consultant (48%, 12/25), or online resources (44%, 11/25). Conclusion: In the largest series to date detailing the breastfeeding experiences of young BC survivors, approximately half of young BC survivors with a successful pregnancy attempted to breastfeed. Among those who had undergone prior lumpectomy and radiotherapy, women reported no milk production or only limited supply from the treated breast. Despite these limitations, most women who attempted to breastfeed were satisfied with their ability to do so. Specific resources to support the experience of breastfeeding in BC survivors are needed. Citation Format: Tal Sella, Kimia Sorouri, Shoshana Rosenberg, Margaret Loucks, Kathryn Ruddy, Shari I. Gelber, Rulla M. Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Ellen Warner, Ann Partridge. Breastfeeding in Survivors of Early Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-06.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701