Quality of Life in the Phase 2/3 Trial of N-803 Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin‒Unresponsive Nonmuscle-Invasive Bladder Cancer

Open AccessUrology PracticePatient Care1 Mar 2024Quality of Life in the Phase 2/3 Trial of N-803 Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin‒Unresponsive Nonmuscle-Invasive Bladder CancerThis article is commented on by the following:Editorial Comment Karim Chamie, Sam S. Chang, Eugene V. Kramolowsky, Mark L. Gonzalgo, Megan Huang, Paul Bhar, Patricia Spilman, Lennie Sender, Sandeep K. Reddy, and Patrick Soon-Shiong Karim ChamieKarim Chamie Department of Urology, University of California, Los Angeles Medical Center, Los Angeles, California , Sam S. ChangSam S. Chang https://orcid.org/0000-0003-2066-9468 Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee , Eugene V. KramolowskyEugene V. Kramolowsky Virginia Urology, Richmond, Virginia , Mark L. GonzalgoMark L. Gonzalgo https://orcid.org/0000-0003-0476-0288 Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida , Megan HuangMegan Huang ImmunityBio, Inc, Culver City, California , Paul BharPaul Bhar ImmunityBio, Inc, Culver City, California , Patricia SpilmanPatricia Spilman https://orcid.org/0000-0003-2626-6475 ImmunityBio, Inc, Culver City, California , Lennie SenderLennie Sender ImmunityBio, Inc, Culver City, California , Sandeep K. ReddySandeep K. Reddy ImmunityBio, Inc, Culver City, California , and Patrick Soon-ShiongPatrick Soon-Shiong *Corresponding Author: Patrick Soon-Shiong, MD, ImmunityBio, Inc, 9920 Jefferson Blvd, Culver City, CA 90232 ( E-mail Address: [email protected] https://orcid.org/0000-0002-4682-8298 ImmunityBio, Inc, Culver City, California View All Author Informationhttps://doi.org/10.1097/UPJ.0000000000000517AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Introduction: In the phase 2/3 study QUILT-3.032 (NCT03022825), the ability of the IL-15RαFc superagonist N-803 (nogapendekin alfa inbakicept) plus bacillus Calmette-Guérin (BCG) to elicit durable complete responses in patients with BCG-unresponsive nonmuscle-invasive bladder cancer (NMIBC) was demonstrated. As a secondary end point, patient-reported outcomes (PROs) were assessed. Methods: Both cohort A patients with carcinoma in situ with or without Ta/T1 disease and cohort B patients with high-grade Ta/T1 papillary disease who received N-803 plus BCG therapy completed the EORTC (European Organization for Research and Treatment of Cancer) Core 30 and Quality of Life NMIBC-Specific 24 questionnaires at baseline and months 6, 12, 18, and 24 on study. Scores were analyzed using descriptive statistics, and multivariable analyses were performed to identify baseline variables associated with PROs. Results: On study, mean physical function (PF) and global health (GH) scores remained relatively stable from baseline for cohorts A (n = 86) and B (n = 78). At month 6, cohort A patients with a complete response reported higher PF scores than those without (P = .0659); at month 12, > 3 as compared with ≤ 3 prior transurethral resections of bladder tumor was associated (P = .0729) with lower GH scores. In cohort B, baseline disease type was associated (P = .0738) with PF and race was significantly associated (P = .0478) with GH at month 6. NMIBC-Specific 24 summary scores also remained stable on study for both cohorts. Conclusions: The overall stability of PROs scores, taken together with the efficacy findings, indicates a favorable risk-benefit ratio and quality of life following N-803 plus BCG. Approximately 80% of newly diagnosed bladder cancers are nonmuscle-invasive (NMIBC).1 Intravesical instillation of bacillus Calmette-Guérin (BCG) after transurethral resection of the bladder tumor (TURBT) is standard of care for intermediate- and high-risk NMIBC patients,2-4 but up to 40% of patients will fail BCG therapy and ∼50% will relapse after an initial response.5-7 While currently there is no standard of care for BCG-unresponsive NMIBC,8 therapies approved by the Food and Drug Administration for BCG-unresponsive NMIBC include pembrolizumab, nadofaragene, combined gemcitabine and docetaxel, and valrubicin.9-11 Radical cystectomy is an option for these patients,12 or it may be suggested they consider participation in a clinical trial. To address the need for a safe, effective therapeutic option for BCG-unresponsive NMIBC patients that provides an opportunity for avoidance of radical cystectomy,12,13 a phase 2/3 clinical trial was conducted wherein intravesical BCG was used in combination with the interleukin-15 superagonist nogapendekin alfa inbakicept (also known as N-803 or Anktiva).14-16 In the study QUILT-3.032, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease (cohort A) and those with high-grade Ta/T1 papillary NMIBC (cohort B) were treated with the investigational therapeutic combination of intravesical N-803 plus BCG. As reported in Chamie et al16 based on data from the January 15, 2022, cutoff, a complete response (CR) was achieved in 71% of cohort A patients with a median duration of 26.6 months, with a high (89.2%) rate of cystectomy avoidance. In cohort B, the median disease-free survival was 19.3 months. The efficacy findings for QUILT-3.032 demonstrate N-803 plus BCG's ability to elicit CRs with a persistence of effect, but given the chronic nature of NMIBC—particularly in the absence of a CR—and the requirement for repeated treatment and endoscopic examinations in this patient population, patient-reported outcomes (PROs) are also an important consideration.17 As part of protocol design for QUILT-3.032, participants were asked to complete both cancer- and NMIBC-specific quality of life (QoL) questionnaires to facilitate more meaningful comparison of N-803 plus BCG therapy to other available therapies and potentially identify variables that may affect PROs. Here, we present findings from the May 16, 2022, cutoff from these questionnaires along with multivariable analyses. Methods Study Participants and Treatment QUILT-3.032 (NCT03022825) is an ongoing registrational, pivotal, open-label, single-arm,18 3-cohort, multicenter trial (32 clinical trial sites) of intravesical N-803 (ImmunityBio, Inc) plus BCG or N-803 alone in patients with BCG-unresponsive NMIBC.16 In cohorts A and C, patients were enrolled with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 papillary disease; cohort B enrolled patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC. Other details of patient inclusion (and exclusion) criteria for enrollment can be found in Chamie et al,16 and the study protocol provided with the Supplementary Materials (https://www.urologypracticejournal.com). Treatments and Assessments Patients in cohorts A and B were treated with intravesical N-803 (400 μg per instillation) plus intravesical BCG (50 mg per instillation). Patients in cohort C received intravesical N-803 monotherapy (400 μg per instillation). All patients received intravesical treatment via a urinary catheter weekly for 6 consecutive weeks during the induction treatment period. Response assessments were completed every 3 months through month 24 and every 6 months from month 24 to month 60 for all cohorts. Cystoscopy was performed at each response assessment. If a CR was not observed at the required week 12 assessment, patients were offered the option of Reinduction Comprising an Additional 6 Weeks of Treatment QoL Assessment QoL was assessed by the EORTC (European Organization for Research and Treatment of Cancer; www.qol.eortc.org) QoL Questionnaire Core 30 (QLQ-C30) and QoL NMIBC-Specific 24 Questionnaire (QLQ-NMIBC24) in cohort A, B, and C patients. The QLQ-C30 is a 30-question widely used cancer-specific health-related QoL questionnaire that comprises a global health (GH) status scale, 5 functional scales (physical, role, emotional, cognitive, and social) and 9 symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). It allows assessment of the patient's perception of their state of well-being, including their ability to perform activities that reflect physical, psychological, and social well-being; as well as the patient's satisfaction with levels of functioning and disease control.19,20 The QLQ-NMIBC24 is a 24-item questionnaire specifically for patients with NMIBC that assesses 11 domains: urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, risk of contaminating partner, sexual intimacy, sexual enjoyment, sexual function, male sexual problems, and female sexual problems. For scoring the QLQ-C30 and QLQ-NMIBC24, raw scores of each domain were calculated by averaging the response scores of comprised items in each domain. A linear transformation was then performed to standardize the raw scores, such that scores for each domain range from 0 to 100. Higher scores indicate higher (better) levels of GH status or functioning, or higher (worse) levels of symptoms. For scoring the QLQ-C30 and QLQ-NMIBC24, raw scores of each functional/symptom domain were calculated by averaging the response scores of comprised items in each domain. A linear transformation was then performed to standardize the raw scores, such that scores for each domain range from 0 to 100. Higher scores indicate higher (better) levels of GH status or functioning, or higher (worse) levels of symptoms.21 Summary scores for GH and physical function (PF) were compared for all patients at 0, 6, 12, 18, and 24 months (questionnaires were not completed at month 3), and for those with CR vs without a CR at 0, 6, and 12 months. Eleven summary scores and 3 individual questions—"do you feel ill or unwell?," "do you feel pain or burning when urinating?," and do you have "worries about repeated bladder treatments?"—from the QLQ-NMIBC24 were also compared at 0, 6, and 12 months. To assess the influence of baseline clinical variables such as age (<65 or ≥65 years), gender (female or male), race (White, non-White), baseline disease type (for cohort A, CIS, CIS/Ta, CIS/T1, and in addition for cohort B, papillary T1), baseline Eastern Cooperative Oncology Group (ECOG) status (0, 1-2), number of prior prestudy BCG doses (<12, ≥12), prior cancer therapy (BCG, BCG plus other therapy), and number of prior TURBTs (≤3, >3), as well as the nonbaseline variable of CR or no CR on GH, PF, and 11 summary scores from the QLQ-NMIBC24, multivariable analyses were performed. In the multivariable regression model used, change from baseline score was the dependent variable, baseline QoL score was included as a covariate, and baseline clinical variables were included as independent variables. The multivariable analyses were conducted on month 6 and 12 scores and significance was established as a P value < .1. The rate of questionnaire completion was determined and, as additional non-PROs that nonetheless reflect QoL, utilization of health care including hospitalizations, opioid use, peripheral red blood cell infusions, and palliative procedures were also recorded. For the QoL and other findings reported here, the data cutoff was May 16, 2022. Missing Data For instances of missing specific items or questions, summary scores were calculated according to the EORTC Scoring Manual, that is, if ≥ half of the component items are missing, the summary score was recorded as missing; otherwise, it was calculated based on the average of the nonmissing item values. Should entire forms be missing, no imputation was performed. Trial Oversight The trial was designed by the sponsor ImmunityBio. Ethics bodies at each participating institution approved the protocol and any amendments. The study was conducted in accordance with the International Conference on Harmonization for Good Clinical Practice guidelines22 and with the principles of the Declaration of Helsinki. Written consent was given by all study participants before enrollment. Data were gathered by study investigators and analyzed by Biostatistics at ImmunityBio. The sponsor, ImmunityBio, vouches for the data. Results The demographics of participants that contributed to the PROs reported here are listed in Supplementary Table S1 (https://www.urologypracticejournal.com). The mean age of cohort A (n = 88) participants was 72.6 years, 88% were male, 90% were White, and 82% had a baseline ECOG status performance of 0. The mean age of cohort B participants (n = 79) was 71.6 years, 73% were male, 89% were White, and 76% had a baseline ECOG status performance of 0. For cohort A, PRO completion rate was high, being 90% at most time points; for cohort B, the QLQ-C30 completion rate declined only slightly after baseline with a greater decline in the completion rate for the QLQ-NMIBC24 (Supplementary Table S2, https://www.urologypracticejournal.com). For the summary of QLQ-C30 questions concerning GH, for both cohorts A and B there was a modest decrease in the mean from baseline at month 6 all that became less by month 12 for cohort B and month 24 for cohort A (Figure 1, A). There was a modest decrease in PF for cohort A at months 12, 18, and 24; PF remained stable for cohort B (Figure 1, B). Figure 1. Global health (GH) and physical function (PF) summary scores. GH (A) and PF (B) summary scores for all participants in cohorts A and B. GH (C) and PF (D) summary scores for all (black), responder (green), and nonresponder (red) cohort A participants at baseline and months 6 and 12. N numbers at each time point are color-coded. Data are graphed as mean and SD. When cohort A responders (those with a CR) were compared with nonresponders, they showed less of a decrease in GH and PF summary scores on study (Figure 1, C and D, respectively), although both parameters were higher at baseline for responders. We note a similar comparison was not made for cohort B because disease-free survival, rather than response to therapy, was the primary outcome for cohort B. Multivariable Analyses of QLQ-C30 Summary Scores In cohort A at month 6, achievement of a CR was associated with higher PF scores as compared with to no CR (P = .0659), and at month 12, > 3 prior TURBTs was associated with lower GH scores as compared with ≤ 3 prior TURBTs (P = .0729; Table 1). For cohort B at month 6, race was significantly associated with GH (P = .0478) and PF was lower for those with CIS/T1 disease as compared with papillary Ta disease (P = .0738). No other baseline variable had significant or a trend for a significant level of association. Table 1. Multivariable Analysis of Global Health and Physical Function Variable Cohort A Cohort B GH PF GH PF Mo 6 Mo 12 Mo 6 Mo 12 Mo 6 Mo 12 Mo 6 Mo 12 P value Est P value Est P value Est P value Est P value Est P value Est P value Est P value Est Age (<65 [ref], ≥65 y) .6428 −2.79 .9199 1.23 .9853 −0.10 .9723 0.32 .9920 −0.08 .6504 3.73 .9907 0.05 .9728 0.26 Sex (F [ref], M) .6077 −4.83 .9638 −0.68 .9110 0.9100 .7454 −3.70 .7828 2.03 .8428 −1.55 .5096 −2.59 .1654 −10.23 Race (White [ref], non-White) .7674 2.69 .8969 −2.39 .3249 −7.07 .9101 −1.30 .0478 24.65 .3752 12.20 .2218 7.96 .4586 9.39 Baseline disease typea CIS/T1 .9474 0.56 .696 7.05 .7149 2.73 .2477 14.53 .8769 2.54 .0738 −15.83 Baseline disease typea CIS/Ta −10.13 .3498 −11.46 .8636 −0.95 .7906 −2.58 Baseline disease type CISb .4144 −18.92 .7492 3.96 Baseline disease typeb T1 .9084 −0.85 .7661 2.54 .2606 −4.45 .8916 1.04 Baseline ECOG (0 [ref], 1-2) .7968 1.90 .5252 −8.82 .8443 −1.34 .2787 −12.16 .1121 −12.82 .9413 −0.79 .8389 0.85 .8024 −2.51 No. prior BCG doses (<12 [ref], ≥12) .4691 −4.45 .1803 16.35 .6797 2.23 .2417 10.65 .8007 1.60 .5319 4.65 .4530 −2.60 .6190 3.39 Prior cancer therapyc .3063 −4.81 .5207 6.58 .2233 −5.00 .9606 0.36 .3413 7.09 .2604 9.74 .2418 4.65 .6643 −3.38 No. prior TURBTs (≤3 [ref[, >3) .5769 −2.71 .0729 −17.69 .4839 3.2 .6346 −3.78 .5417 −4.08 .6270 −3.74 .5611 −2.10 .6559 3.23 CRd or no CR [ref] .3324 5.36 .4396 8.3 .0659 9.18 .489 5.98 Abbreviations: BCG, bacillus Calmette-Guérin; CIS, carcinoma in situ; CR, complete response (not baseline); ECOG, Eastern Cooperative Oncology Group; Est, estimate; F, female; GH, global health; M, male; PF, physical function; ref, reference; TURBT, transurethral resection of bladder tumor. Bolded P values indicate < .05 level of significance. Cohort A (reference group is CIS). Cohort B (reference group is high Ta). BCG only (reference), BCG + other therapy. CR vs no CR not performed for cohort B. QLQ-NMIBC24 Summary Scores For cohort A overall, summary scores for the QLQ-NMIBC24 questionnaire concerning urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual function, sexual intimacy, risk of contaminating partner, sexual enjoyment, and sexual problems (male, female) remained stable from baseline to months 6 and 12 (Figure 2, A). Figure 2. Quality of Life Nonmuscle-Invasive Bladder Cancer‒Specific 24 Questionnaire (QLQ-NMIBC24) summary scores. Cohorts A (A) and B (B) summary scores at 0 (baseline), 6, and 12 months on study regarding the questions listed on right side of figure are shown. Data are graphed as mean and SD. For cohort B, summary scores similarly remained stable, with sexual problems for female participants decreasing at months 6 and 12 (Figure 2, B), noting that—particularly for month 12—n numbers were low and statistical significance was not achieved (Supplementary Table S3, https://www.urologypracticejournal.com). In response to the QLQ-NMIBC24 question, "Did you feel ill or unwell?" there was an increase of the response "a little" at month 6 for cohort A patients, but responses returned to near baseline levels at months 12, 18, and 24; responses remained stable in cohort B (Table 2). Table 2. Did You Feel Ill or Unwell? Cohort A Cohort B Baseline 6 mo 12 mo 18 mo 24 mo Baseline 6 mo 12 mo 18 mo 24 mo Total No. 86 66 50 46 35 77 58 38 27 19 Not at all, No. (%) 82 (95.35) 58 (87.88) 46 (92.00) 43 (93.48) 32 (91.43) 71 (92.21) 55 (94.83) 37 (97.37) 25 (92.59) 18 (94.74) A little, No. (%) 4 (4.65) 8 (12.12) 3 (6.00) 2 (4.35) 2 (5.71) 5 (6.49) 3 (5.17) 1 (2.63) 1 (3.70) 1 (5.26) Quite a bit, No. (%) 0 0 1 (2.00) 1 (2.17) 0 1 (1.30) 0 0 1 (3.70) 0 Very much, No. (%) 0 0 0 0 1 (2.86) 0 0 0 0 0 For the QLQ-NMIBC24 question, "Have you had any pain or a burning feeling when urinating?" the percentage of patients reporting "not at all" increased from baseline at all on-study time points (6, 12, 18, and 24 months; Supplementary Table S4, https://www.urologypracticejournal.com) in both cohorts A and B. In response to the question, "Did you worry about having repeated bladder treatments (cystoscopies or instillations)?" cohort A patient responses remained stable at ∼50% "not at all" until month 24 when the n had dropped from 86 at baseline to 11, and that response dropped to 36% (n = 4) with 55% (n = 6) responding "a little" (Supplementary Table S5, https://www.urologypracticejournal.com). In cohort B, the percent responding "not at all" decreased from 44% (n = 32) at baseline to 32% (n = 13) at month 6 and 38% (n = 9) at month 12, but increased to 63% (n = 12) and 80% (n = 4) at months 18 and 24, respectively. While baseline QoL scores were assessed for cohort C patients (n = 10), due to the lack of efficacy of N-803 monotherapy, there were only 3 and 1 cohort C participant(s) by months 6 and 12 of the study, respectively. The collected data is not presented as the low n numbers render interpretation difficult. Multivariable Analysis of QLQ-NMIBC24 Summary Scores Several variables were significantly associated with QLQ-NMIBC24 summary scores (Table 3). In cohort A patients, age was associated with decreased urinary symptoms and intravesical treatment issues at month 12. Male gender was associated with urinary symptoms at month 12 and sexual intimacy at month 6. Race (non-White) was associated with decreased malaise and increased reported sexual intimacy at month 6. Also in cohort A, decreased sexual intimacy was also associated with disease type and number of prior TURBTs at month 6; disease type was also associated with increased reporting of bloating and flatulence at month 12. Achievement of a CR was associated with better scores for questions related to sexual activity, including sexual function, intimacy, and problems. Table 3. Multivariable Analysis of Quality of Life Nonmuscle-Invasive Bladder Cancer‒Specific 24 Questionnaire Summary Scores Question Variable Cohort A Cohort B P value, mo 6 Est P value, mo 12 Est P value, mo 6 Est P value, mo 12 Est Urinary symptoms Age (<65, ≥65 y [ref]) .0238 −23.03 Sex (F, M [ref]) .0287 26.76 Baseline ECOG (1-2) .0608 21.14 Racea .0628 −26.31 Malaise Racea .0470 −6.21 BCG + other therapyb .0582 3.4 Future worries Age (<65, ≥65 y [ref]) .0375 −16.91 No. prior TURBT (≤3, >3 [ref]) .0690 9.89 Baseline disease type T1 .0187 20.86 Baseline ECOG (1-2) .0221 −25.98 Bloating & flatulence Baseline disease typec CIS/T1 .0090 −25.91 Intravesical Tx issues BCG + other therapyb .092 8.13 Age (<65, ≥65 y [ref]) .0412 −26.64 .0300 −18.74 Sex (F, M [ref]) .0702 −14.64 Racea .0290 −31.14 Baseline disease type T1 .0458 17.65 Sexual function Age (<65, ≥65 y [ref]) .0865 −13.51 No. prior TURBT (≤3, >3 [ref]) .0644 −10.24 .0794 −14.39 Sex (F, M [ref]) .0976 14.30 CR [ref] or no CRd .0110 16.65 .0364 22.87 Sexual intimacy Sex (F, M [ref]) .0316 −109.48 Racea .0224 89.87 Baseline disease typec CIS/T1 .0846 −41.83 Baseline disease type CIS/Ta [ref] .0365 −50.65 No. prior TURBT (≤3, >3 [ref]) .0170 −58.82 CR [ref] or no CRd .0137 75.82 Sexual enjoyment Baseline disease type CIS/Ta .0574 −51.76 No. prior TURBT (≤3, >3 [ref]) .0693 −85.09 BCG + other therapyb .0602 70.45 Sexual problems, M Baseline disease type CIS .0268 −75.33 Baseline ECOG (1-2) .0488 −25.30 Baseline disease type CIS/Ta .0700 21.84 CR [ref] or no CRd .0153 −30.60 Abbreviations: BCG, bacillus Calmette-Guérin; CIS, carcinoma in situ; CR, complete response (not baseline); ECOG, Eastern Cooperative Oncology Group; Est, estimate; F, female; M, male; ref, reference; TURBT, transurethral resection of bladder tumor. White vs non-White (ref). BCG only. CIS vs CIS/Ta (ref), CIS/T1 (ref). CR (not baseline). Overall, there were more significant changes in cohort A PROs in areas related to sexual activity, whereas there were more significant changes in cohort B PROs regarding future worries and intravesical treatment issues. Health Care Utilization As shown in Supplementary Table S6 (https://www.urologypracticejournal.com), hospitalizations were low during the course of the study, between 1% to 6% for cohort A and 1% to 5% for cohort B up to 12 months. Opioid use related to bladder cancer increased after months 6 to 7 in cohort A and after month 2 to 3 in cohort B, although was near baseline at some time points during this period. Palliative procedures increased to 5% at months 10 to 11 in both cohorts A and B, representing 2 subjects in each. Discussion The finding of relative stability of GH and PF during the course of the study is similar to that reported by Catto et al23 and described by others24,25 for BCG monotherapy, suggesting combination N-803 plus BCG intravesical therapy is at least as tolerable as treatment with BCG alone. Perhaps not unexpectedly, achievement of a CR was associated with higher patient-reported GH and PF scores and the higher (although not significantly) scores at baseline for those that would go on to achieve a CR possibility suggests better overall health at baseline that may increase the opportunity of a CR. Analysis of non-PRO baseline clinical variables that might be associated with achievement of a CR is ongoing. Summary scores for the NMIBC-specific questionnaire, an important assessment for determining effects for this particular patient population, also remained stable through 12 months. The answers to these questions may reveal a difference in concerns and priorities in patients with different NMIBC disease types, with those having the less advanced CIS disease in cohort A reporting changes in sexual function and activity, while those with the more progressed high-grade papillary disease in cohort B appearing to focus more on future worries and intravesical treatment issues. The absence of comparison of PROs for patients receiving BCG plus N-803 combination therapy to BCG alone may be considered a limitation of the data presented herein. We note, however, that QUILT-3.032 was designed as a nonrandomized trial based on the recommendation of the Food and Drug Administration18 that—given the futility of additional BCG monotherapy in BCG-unresponsive patients13—a BCG monotherapy comparator group should not be used. Therefore, the findings may be considered descriptive, but nonetheless informative. Conclusions The patient-reported QoL assessment in QUILT-3.032, considered together with the relatively low on-study hospitalization rate and—as reported in Chamie et al16—the observation that 86% of treatment-emergent adverse events were grade 1 to 2 with only 3 grade 3 immune-related treatment-emergent adverse events, supports the safety of N-803 plus BCG combination therapy. When efficacy is also considered, not only the 71% CR rate but also the high Kaplan-Meier estimated probability of cystectomy avoidance of 89.2% at 24 months in patients with a CR, treatment of BCG-unresponsive NMIBC with N-803 plus BCG can be viewed as having a favorable risk-benefit ratio. References 1. . Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016; 196(4):1021-1029. Link, Google Scholar 2. . Best practice in the treatment of nonmuscle invasive bladder cancer. Ther Adv Urol. 2012; 4(1):13-32. Crossref, Medline, Google Scholar 3. . 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Impact of effective intravesical therapies on quality of life in patients with non-muscle invasive bladder cancer: a systematic review. Int J Environ Res Public Health. 2022; 19(17):10825. Crossref, Medline, Google Scholar Support: The QUILT-3.032 study was funded by ImmunityBio, Inc. Conflict of Interest Disclosures: All Authors with an ImmunityBio, Inc, affiliation are employees of ImmunityBio, Inc. S.C. is a consultant for ImmunityBio, Inc. The other authors have nothing to disclose. Ethics Statement: In lieu of formal ethics committee review, the principles of the Helsinki Declaration were followed. All patients provided informed consent. Author Contributions: K.C. is the principal investigator on the clinical study; S.S.C., E.V.K., and M.L.G. are co-investigators; M.H. and P.B. collected and performed biostatistics on QoL data from the study; P.S. graphed data, created figures and tables, and wrote the first draft of the manuscript; L.S., S.K.R., and P.S.-S. designed the study. All authors contributed to content of and edited the manuscript. Data Availability: All data generated or analyzed during this study are included in this published article (and its supplementary information files). © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySmith A (2024) Editorial CommentUrology Practice, VOL. 11, NO. 2, (375-375), Online publication date: 1-Mar-2024.Related articlesUrology Practice20 Feb 2024Editorial Comment Volume 11Issue 2March 2024Page: 367-375Supplementary Materials Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Keywordsbacillus Calmette-GuérinN-803nonmuscle-invasive bladder cancerBCG-unresponsive NMIBCquality-of-lifeMetrics Author Information Karim Chamie Department of Urology, University of California, Los Angeles Medical Center, Los Angeles, California More articles by this author Sam S. Chang Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee More articles by this author Eugene V. Kramolowsky Virginia Urology, Richmond, Virginia More articles by this author Mark L. Gonzalgo Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Megan Huang ImmunityBio, Inc, Culver City, California More articles by this author Paul Bhar ImmunityBio, Inc, Culver City, California More articles by this author Patricia Spilman ImmunityBio, Inc, Culver City, California More articles by this author Lennie Sender ImmunityBio, Inc, Culver City, California More articles by this author Sandeep K. Reddy ImmunityBio, Inc, Culver City, California More articles by this author Patrick Soon-Shiong ImmunityBio, Inc, Culver City, California *Corresponding Author: Patrick Soon-Shiong, MD, ImmunityBio, Inc, 9920 Jefferson Blvd, Culver City, CA 90232 ( E-mail Address: [email protected] More articles by this author Expand All Support: The QUILT-3.032 study was funded by ImmunityBio, Inc. Conflict of Interest Disclosures: All Authors with an ImmunityBio, Inc, affiliation are employees of ImmunityBio, Inc. S.C. is a consultant for ImmunityBio, Inc. The other authors have nothing to disclose. Ethics Statement: In lieu of formal ethics committee review, the principles of the Helsinki Declaration were followed. All patients provided informed consent. Author Contributions: K.C. is the principal investigator on the clinical study; S.S.C., E.V.K., and M.L.G. are co-investigators; M.H. and P.B. collected and performed biostatistics on QoL data from the study; P.S. graphed data, created figures and tables, and wrote the first draft of the manuscript; L.S., S.K.R., and P.S.-S. designed the study. All authors contributed to content of and edited the manuscript. Data Availability: All data generated or analyzed during this study are included in this published article (and its supplementary information files). Advertisement Advertisement PDF downloadLoading ...