Ashling Wahner

Darzalex Regimen Boosts Rates of MRD Negativity in Newly Diagnosed, Transplant-Eligible Myeloma

Darzalex (daratumumab) plus Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (D-VRd), followed by autologous stem cell transplant (ASCT), D-VRd consolidation (treatment after ASCT) and Darzalex plus Revlimid (DR) maintenance improved rates of sustained minimal residual disease (MRD; measure of remaining cancer cells after treatment) negativity compared with VRd induction, ASCT, VRd consolidation and Revlimid maintenance in transplant-eligible patients with newly diagnosed multiple myeloma, according to updated data from the phase 3 PERSEUS trial.

Findings, which were presented at the 2024 SOHO Annual Meeting, showed that among patients in the D-VRd arm (355 patients), 57.5% were MRD negative at a 10

sensitivity (extremely low) at the end of consolidation vs 32.5% of patients in the VRd arm (354 patients). In the experimental arm, the MRD-negative rates at the 10

 threshold at up to 12 months, up to 24 months, and up to 36 months were 65.1%, 72.1% and 74.6%, respectively. These respective rates were 38.7%, 44.9% and 46.9% in the control arm.

sensitivity, the MRD-negativity rates (no detectable cancer cells) in the D-VRd arm at the end of consolidation, up to 12 months, up to 24 months and up to 36 months were 34.4%, 43.9%, 57.7% and 63.9%, respectively. In the VRd arm, these respective rates were 16.1%, 20.9%, 27.4% and 30.8%.

D-VRd significantly increased MRD negativity rates.

Patients receiving D-VRd maintained MRD-negative status longer.

D-VRd outperformed VRd in reducing residual cancer cells and improving survival.

D-VRd could become a new standard of care for transplant-eligible patients.

Treatment was tailored to individual patients' MRD status.

Furthermore, 64.8% of patients in the D-VRd group sustained MRD negativity at the 10

threshold for at least 12 months compared with 29.7% of patients in VRd arm. The rates of patients who sustained MRD negativity for at least 18 months at 10

 were 59.4% and 25.1%, respectively. At a 10

 sensitivity, 47.3% of patients in the D-VRd arm sustained MRD negativity for at least 12 months vs 18.6% of patients in the VRd arm. The respective rates of patients who sustained MRD negativity for at least 18 months in these arms were 42% and 15%.

“These data further highlight the benefit of D-VRd and DR maintenance as a new standard of care for transplant-eligible patients with newly diagnosed multiple myeloma,” presenting study author Dr. Meletios A. Dimopoulos said during the presentation.

A New Treatment Option for Transplant-Eligible, Newly Diagnosed Myeloma

 for induction and consolidation in patients with newly diagnosed multiple myeloma who are candidates for ASCT, based on prior data from PERSEUS.2

Previous findings demonstrated that D-VRd reduced the risk of disease or death by 58% compared with VRd alone. The 48-month progression-free survival (PFS; how long a patient with cancer lives without their disease getting worse) rate was 84.3% with D-VRd vs 67.7% with VRd.

The phase 3 study included patients 18 to 70 years of age with newly diagnosed multiple myeloma who were eligible for ASCT.

Patients were randomly assigned to a specific treatment prior to the start of induction therapy. In the control arm, patients received VRd prior to ASCT. Those in the experimental arm received Darzalex plus the same VRd regimen prior to transplant. Induction therapy was given for four 28-day cycles. After ASCT, D-VRd or VRd were administered at the same dosages for two additional cycles.

During ongoing treatment, patients in the control arm received Revlimid until disease progression. In the experimental arm, ongoing therapy was based on MRD status; all patients initially received Darzalex plus Revlimid for a minimum of two years. Patients who were MRD positive continued DR. Those who were MRD negative for at least 12 months and achieved a complete response (CR; when a person's disease cannot be detected by any tests or examinations) or better continued with Revlimid alone; they were permitted to restart Darzalex if they lost their CR without progressive disease or became MRD positive.

PFS served as the trial’s primary outcome. Secondary outcomes included overall CR or better rate, overall MRD-negativity rate and overall survival (OS; the time from the start of treatment when a patient with cancer is still alive).

Subgroup analyses showed that D-VRd improved MRD-negativity rates and sustained MRD-negativity rates compared with VRd across predefined groups.

The overall stringent CR (sCR; a more rigorous standard compared with traditional CR), CR, very good partial response (VGPR; cancer shrank significantly but still present) and PR rates in the D-VRd arm were 69.3%, 18.6%, 7.3% and 1.4%, respectively. These respective rates were 44.6%, 25.4%, 19.2% and 4.5% in the control arm. The CR or better rate was 87.9% in the D-VRd arm vs 70.1% in the VRd arm.

In the D-VRd arm, the respective sCR, CR, VGPR and PR rates at the end of induction were 9.6%, 13%, 62.3% and 9.3%. After ASCT, these rates were 10.7%, 17.2%, 57.5% and 8.7%, respectively. At the end of induction, the sCR, CR, VGPR and PR rates were 18.9%, 25.6%, 46.5% and 4.2%, respectively.

For the VRd arm, the sCR, CR, VGPR and PR rates at the end of induction were 7.1%, 14.1%, 51.4% and 18.1%, respectively. After ASCT, these respective rates were 8.2%, 15.3%, 50% and 17.5%. Following consolidation, the sCR, CR, VGPR and PR rates were 13%, 21.8%, 47.5% and 9.9%, respectively.

Among patients with high-risk disease, those treated with D-VRd (76 patients) achieved an MRD-negativity rate of 68.4% at the 10

 threshold. Those rates were 47.4% and 30.8%, respectively, among patients with high-risk disease in the VRd arm (78 patients). In the experimental arm, 48.7% of patients maintained MRD negativity at a 10

sensitivity for at least 12 months and 30.3% remained MRD negative at the 10

threshold for at least 12 months. Those respective rates were 25.6% and 14.1% in the control arm.

D-VRd (44 patients) also trended toward improved PFS among patients with high-risk disease who achieved MRD negativity at a 10

sensitivity compared with those treated with VRd (24 patients)

Among patients in the D-VRd arm who were MRD positive at the end of consolidation (88 patients), 60.2% became MRD negative at the 10

threshold during maintenance compared with 40.5% of patients treated with VRd (121 patients). At the 10

threshold, these rates were 56.7% for D-VRd (134 patients) and 25.2% for VRd (155 patients). Among patients who became MRD negative at a 10

 sensitivity, 38.6% in the D-VRd arm had sustained MRD negativity vs 17.4% in the control arm. At the 10

 sensitivity, these respective rates were 31.3% and 10.3%.

 sensitivity was associated with improved long-term outcomes in both arms. Overall, 65.1% of patients in the D-VRd arm reached MRD negativity at the 10

threshold at any point compared with 32.2% of patients in the VRd arm.

“The percentage of patients achieving MRD negativity with D-VRd was significantly higher. This again speaks in favor of administering [D-VRd] up-front in order to increase the number of patients who will achieve MRD negativity, sustained MRD negativity, improved PFS and hopefully improved OS,” Dimopoulos concluded.

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Articles

A Darzalex-based regimen improved MRD negativity rates compared with VRd in patients with newly diagnosed, transplant-eligible multiple myeloma.

Darzalex Regimen Boosts Rates of MRD Negativity in Newly Diagnosed, Transplant-Eligible Myeloma 

Conjugated equine estrogen was associated with higher gynecologic cancer death rates in certain patients.

For patients with ovarian and endometrial cancer, receiving conjugated equine estrogen (CEE; a drug that includes estrogen hormones to treat menopause symptoms) alone was associated with significantly increased cancer-related mortality rates, compared with placebo (inactive treatment) in postmenopausal women who had undergone a prior hysterectomy (surgical removal of the uterus), according to 20-year follow-up data from 2 Women’s Health Initiative (WHI) clinical trials presented during a 

Findings from another randomized study also found that in postmenopausal women with a uterus, CEE in combination with medroxyprogesterone acetate (MPA; menopausal hormone therapy) was not associated with increased ovarian cancer mortality versus placebo — a finding that contrasted data from prior observational studies.

In 2023, endometrial and ovarian cancer accounted for 13,030 and 13,270 deaths, respectively, in the United States, according to a study published in 

“CEE and MPA were approved [as] hormone therapy in the United States [US] in 1943, and the question about endometrial and ovarian cancer has since remained unsettled after nearly 50 years of follow-up,” Dr. Rowan T. Chlebowski, said during the press briefing.

Chlebowski is an investigator at The Lundquist Institute, as well as chief of the Division of Medical Oncology and Hematology at the Harbor-University of California, Los Angeles (UCLA) Medical Center and a professor of medicine at the David Geffen School of Medicine at UCLA.

 included data from two randomized, placebo-controlled, WHI clinical trials that were conducted at 40 clinical centers in the US and enrolled patients from 1993 to 1998. The first trial enrolled 10,739 postmenopausal women who had undergone a prior hysterectomy and received either CEE or placebo.

The second trial enrolled 16,608 postmenopausal women with an intact uterus who received either CEE plus MPA or placebo. Patients were eligible for inclusion in either study if they were 50 to 79 years of age and had no history of breast cancer, with protocol-mandated annual mammogram findings that were not suggestive of breast cancer and endometrial biopsies that were not suggestive of endometrial cancer.

“We only did a study with endometrial cancer in the women who got CEE plus MPA because we had previously known about the increased risk of endometrial cancer in women getting estrogen alone,” Chlebowski noted.

In the CEE-alone trial, ovarian cancer developed in 35 patients who received CEE alone, compared with 17 of those who received placebo. In these respective populations, ovarian cancer mortality occurred in 25 and nine patients, and death from all causes after ovarian cancer occurred in 30 and 12 patients.

“This is the first randomized clinical trial with evidence to indicate that ovarian cancer mortality is increased by [use of] estrogen alone,” Chlebowski emphasized.

In the CEE-plus-MPA trial, ovarian cancer developed in 75 patients who received CEE plus MPA versus 63 of those who received placebo. In these respective populations, ovarian cancer mortality occurred in 65 and 52 patients. Death from all causes after ovarian cancer occurred in 68 and 48 patients.

Endometrial cancer developed in 106 patients who received CEE plus MPA versus 140 of those who received placebo. In these respective populations, endometrial cancer mortality occurred in 13 and 21 patients, and death from all causes after endometrial cancer occurred in 51 and 72 patients.

“These findings inform decisions regarding hormone therapy use and suggest reconsideration of guideline recommendations regarding [the use of] estrogen alone in [postmenopausal women],” Chlebowski concluded.

Postmenopausal patients with ovarian or endometrial cancer who received conjugated equine estrogen may have increased mortality rates. 

Conjugated Equine Estrogen Increases Gynecologic Cancer Death Rates

Patients with blood cancer who were given Orca-T to prevent post-transplantation graft-versus-host disease (GVHD) tended to have better survival than those treated with post-transplant cyclophosphamide (PTCy), according to recent findings presented at the 2024 Transplantation & Cellular Therapy Meetings.

Of note, all patients had matched unrelated donors and were undergoing myeloablative conditioning (MAC), which delays an immune response to the donor cells.

Compared to traditional post-transplant cyclophosphamide (PTCy), Orca-T tends to result in better survival rates and lower rates of post-transplant complications.

The study, presented at the 2024 Transplantation & Cellular Therapy Meetings, found that Orca-T led to a 77% relapse-free survival rate and a 94% overall survival rate, compared to 62% and 77% respectively with PTCy.

These findings highlight the importance of identifying effective treatments to improve outcomes for patients undergoing stem cell transplantation, where over 40% face mortality within three years due to various complications.

Ongoing research, including the Orca Precision-T trial, aims to further evaluate Orca-T's effectiveness in different patient populations and refine its use in clinical practice.

The relapse-free survival (RFS; time patients lived without experiencing relapse) rate was 77% in the cohort of patients who received Orca-T vs 62% in the cohort of patients who received PTCy. Furthermore, the non-relapse mortality (NRM; post-transplant death without relapse or recurrent diseaes) rates with Orca-T and PTCy were 3% and 16%, respectively, and the overall survival (OS; percentage of patients who are still alive) rates were 94% and 77%, respectively.

“The positive impact [of Orca-T] on RFS, NRM and OS highlight the importance of identifying treatment approaches that may be beneficial across all key transplant outcomes in addition to the reduction of [chronic] GVHD,” Dr. Alexandra Gomez Arteaga, lead study author and an assistant professor of Medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine/New York-Presbyterian Hospital in New York, New York, stated in the presentation.

Although progress has been made in the treatment of patients with hematologic malignancies requiring allogeneic stem cell transplantation, over 40% of patients who receive allogeneic hematopoietic stem cell transplant (HSCT) die within the first three years of receiving this treatment, with most deaths caused by primary relapse (53%), infection (14%), GVHD (13%) and organ failure (13%). However, Orca-T cell therapy may improve clinical outcomes for these patients.

In the phase 3 BMT CTN 1703 trial, significantly higher GVHD-free RFS rates were observed with PTCy/mycophenolate mofetil/tacrolimus prophylaxis compared with standard prophylaxis in patients who received reduced-intensity conditioning.In the myeloablative setting, however, outcomes in the PTCy arm were not different than those with tacrolimus plus methotrexate. Despite these findings, the use of PTCy in the MAC setting has increased, and NRM and relapse risk continue to be drivers of PTCy progression.

This retrospective study compared historical outcomes with Orca-T vs PTCy in patients who received peripheral blood stem cell (PBSC) grafts and MAC. The Orca-T cohort (111 patients) used clinical data from a multicenter phase 1b trial of Orca-T plus single-agent tacrolimus, which had primary end points of the incidence and timing of primary graft failure and the incidence and timing of moderate to severe (grade 3/4) acute GVHD.

Patients were at least 18 years of age, with a median age of 49 years (range, 20-65). Primary diseases included acute leukemia in complete remission (CR; no detectable disease) or CR with incomplete hematologic recovery (CRi; acute myeloid leukemia [AML; 45.9%], acute lymphoblastic leukemia [ALL; 33.3%], and mixed phenotype [1.8%]), myelodysplastic syndrome (MDS; 15.3%), or chronic myeloid leukemia (CML; 3.6%) treated with Orca-T between 2019 and 2022.

Patients were required to have 8/8 matched related or unrelated donors, and 50.5% of patients had matched related donors. Forty-seven percent of patients were female, and patients had a hematopoietic cell transplantation–specific comorbidity index (HCT-CI; a scale used to predict prognosis) of up to 4 and a Karnofsky performance score (KPS) of at least 70, indicating that they can do most of their daily tasks independently. The median follow-up in this trial was 17 months.

Investigators found no difference in outcomes between matched unrelated donors and matched sibling donors with Orca-T in this trial.

Data from patients who underwent Orca-T treatment were compared to another cohort (83 patients), which consisted of data from a publicly available dataset from the Center for International Blood & Marrow Transplant Research (CIBMTR) database, which included 284 MUD transplantations with PTCy GVHD prophylaxis.

Patients were at least 18 years of age, with a median age of 52 years (range, 18-71). Primary diseases included ALL (26.5%), AML (49.4%), and MDS (24.1%). Forty-nine percent of patients were female, and all patients had 8/8 matched unrelated donors. The primary end point of this dataset was OS, and patients had a median follow-up of 12 months. The limitations to this CIBMTR dataset were that it included only matched unrelated donors, the treatment time frame was from 2011 to 2018, and the incidence of chronic GVHD (cGVHD) was not reported by grade, so investigators were unable to delineate the percentages of moderate and severe GVHD in this population.

The key outcomes assessed in this retrospective analysis were RFS, NRM and OS.

In the myeloid subgroup of the Orca-T cohort (48 patients), the median age was 54 years (range, 20-64) and the median follow-up was 15 months. Forty-eight percent of patients were female, and 58% had HLA-matched related donors. Additionally, 77.1% had ALL and 22.9% had MDS.

In the myeloid subgroup of the PTCy cohort (61 patients), the median age was 57 years (range, 20-71) and the median follow-up was 12 months. Forty-nine percent of patients were female, and 100% had HLA-matched unrelated donors. Additionally, 67.2% had ALL and 32.8% had MDS.

In the myeloid subgroups of the Orca-T and PTCy cohorts, the respective RFS rates were 86% and 63%, the respective NRM rates were 0% and 17%, and the respective OS rates were 100% and 76%.

Investigators found that older age was associated with higher NRM rates with PTCy but not with Orca-T. At 12 months, the NRM rates in patients with myeloid diseases who were younger than 55 years of age were 0% and 8.5% in the Orca-T and PTCy subgroups, respectively. These rates were 0% and 24%, respectively, in patients with myeloid diseases who were older than 55 years of age.

Limitations of this research include its retrospective, nonrandomized design. In the future, investigators plan to evaluate Orca-T vs PTCy in the MAC setting in contemporary homogenous patient populations that include 8/8 matched related and unrelated donors and comparable PBSC donor sources.

Long-term follow-up of this future research at two years and beyond will further demonstrate the differences in key clinical outcomes between treatment with Orca-T and PTCy, including relapse, GVHD, infections, organ toxicities, engraftment syndrome and length of hospitalization and hospital readmissions.

“Acknowledging the limitations of historical comparisons and retrospective analyses, Orca-T could potentially provide improved outcomes as compared with PTCy-based MAC with PBSC graft in patients with acute leukemia or MDS,” Gomez-Arteaga concluded.

The randomized phase 3 Orca Precision-T trial is currently enrolling patients across the United States with undifferentiated AML, ALL or mixed-phenotype acute leukemia who are in CR or CRi to their last line of therapy, as well as patients with high-risk, therapy-related MDS, including those with active disease at the time of transplant. Patients must be planned to undergo myeloablative allogeneic HSCT including one of the following MAC regimens: busulfan plus fludarabine and thiotepa, total body irradiation (TBI) plus etoposide, or TBI plus cyclophosphamide. Additionally, patients must be ages 18 to 65 and have an 8/8 matched related or unrelated donor, an HCT-CI of up to 4, a KPS of at least 70, and adequate organ function.

Patients will be randomly assigned to receive either Orca-T plus single-agent tacrolimus prophylaxis (87 patients) or standard unmanipulated allograft plus dual-agent tacrolimus and methotrexate prophylaxis (87 patients). cGVHD-­free survival will serve as the primary end point of the trial, and secondary end points will include GVHD-free RFS, moderate-to-severe cGVHD and RFS.

Orca-T outperformed post-transplant cyclophosphamide when it came to relapse-free survival and overall survival in patients with blood cancer who underwent a stem cell transplantation from a matched unrelated donor. 

Orca-T Improves Post-Transplant Survival in Patients With Blood Cancers

Postsurgical Keytruda (pembrolizumab) tended to lengthen the time patients lived without relapse or complications from their cancer — a statistic known as “disease-free survival” (DFS) — compared to observation in patients with locally advanced urothelial carcinoma (bladder cancer), according to data from the phase 3 AMBASSADOR Alliance A031501 trial.

Keytruda showed promise in extending disease-free survival for patients with locally advanced urothelial carcinoma (bladder cancer) after surgery, compared to observation alone.

The positive effects of Keytruda were observed irrespective of the PD-L1 status, a pathway in cancer cells that Keytruda targets to enhance the immune system's ability to combat cancer.

While the trial met its main goal, the overall survival endpoint — which is the time patients live before death of any cause — did not show a significant difference, potentially influenced by patients in the observation group later receiving a checkpoint inhibitor.

The AMBASSADOR trial, which compared Keytruda to observation, closed early due to the FDA approval of adjuvant Opdivo for high-risk urothelial carcinoma in August 2021.

Keytruda demonstrated benefits across various patient subgroups, except for those with a primary tumor site in the upper tract, which requires further investigation.

Keytruda’s benefit was observed regardless of PD-L1 status, according to findings presented at the 

2024 ASCO Genitourinary Cancers Symposium

. PD-L1 is part of the PD-1 pathway found on cancer cells that Keytruda inhibits. In doing so, the immune system is better able to find and fight cancer.

At a median follow-up of 22.3 months, the median DFS with Keytruda in the intention-to-treat population was 29 months versus 14 months with.

However, at a median follow-up of 36.9 months, the median overall survival (OS; time patients live before death of any cause) was 50.9 months with Keytruda versus 55.8 months with observation.

“The trial met its efficacy end point and is a positive trial,” Dr. Andrea B. Apolo, of the National Institutes of Health in Bethesda, Maryland, stated in a presentation of the data. “The OS end point was not met at interim analysis. It may have been impacted by the high number of patients in the observation arm receiving a checkpoint inhibitor.”

Although the standard of care for patients with muscle-invasive urothelial carcinoma (MIUC) is radical surgery with or without postsurgical cisplatin-based chemotherapy, many patients are not eligible for cisplatin or have persistent muscle-invasive disease after neoadjuvant chemotherapy and surgery. Furthermore, cisplatin-based therapy in the adjuvant setting is not recommended for patients who have received neoadjuvant chemotherapy and is associated with side effects and administration difficulties post-radical surgery in patients not treated with neoadjuvant chemotherapy.

The AMBASSADOR trial assessed the PD-1 checkpoint inhibitor Keytruda versus observation in patients with high-risk MIUC, including cancers of the bladder, renal pelvis, urethra and ureter.Patients must have received radical surgery, including cystectomy, nephrectomy, nephroureterectomy or ureterectomy, more than four but no more than 16 weeks before trial initiation

AMBASSADOR closed early because of the August 2021 FDA approval of adjuvant Opdivo (nivolumab) for patients with high-risk urothelial carcinoma.

Patients in AMBASSADOR were randomly assigned to either Keytruda (354 patients) every three weeks for one year (18 cycles) or observation (348 patients).

DFS and OS served as the main areas assessed by researchers. Other areas of interest included DFS and OS by PD-L1 status and safety. Researchers also assessed DFS and OS by circulating tumor DNA (ctDNA) status; DFS and OS by immune gene signatures; DFS and OS by tumor molecular subtype; DFS and OS by T-cell receptor clonality; and quality of life.

A total of 131 and 126 OS events occurred in the Keytruda and observation arms, respectively. Patients in the Keytruda arm received a mean of 11 treatment cycles. All patients enrolled in the trial are currently not receiving study treatment.

All prespecified patient subgroups benefitted from Keytruda versus observation, except for those with a primary tumor site of the upper tract.

“The upper tract subgroup I think needs further investigation, and the magnitude of benefit is unclear,” Apolo noted.

In patients with PD-L1–positive disease, defined as those with a PD-L1 combined positive score (CPS) of at least 10%, the median DFS was 32.8 months with Keytruda versus 20.7 with placebo. In patients with PD-L­1–negative disease, the median DFS was 22.1 months with Keytruda vs 9.1 months with placebo. Regarding OS differences between prespecified patient subgroups, the HR in the subgroup whose primary site was in the upper tract was 1.45.

The median OS in patients with PD-L1–positive disease was not reached (meaning that researchers could not analyze this outcome because more than half of patients were alive) with Keytruda versus 56.1 months with observation. The median OS in patients with PD-L1–negative disease was 43.8 months with Keytruda versus 36.7 months with observation.

“PD-L1 positivity using the CPS was associated with a better prognosis but was not predictive for treatment efficacy,” Apolo emphasized. “PD-L1 status should not be used to select patients for treatment.”

Among the patients in the Keytruda arm who did not withdraw consent, 99 received alternative systemic therapy. Patients were permitted to report multiple alternative treatments. In the post-DFS setting, 82 patients received alternative systemic therapy, including a checkpoint inhibitor (19 patients), chemotherapy (38 patients), antibody-drug conjugates (ADCs; 45 patients), and other therapy (four patients). In the pre-DFS setting, 17 patients received alternative systemic therapy, including a checkpoint inhibitor (six patients), chemotherapy (four patients) and ADCs (three patients).

Among the patients in the observation arm who did not withdraw consent, 123 received alternative systemic therapy. In the post-DFS setting, 104 patients received alternative systemic therapy, including a checkpoint inhibitor (76 patients), chemotherapy (34 patients), ADCs (21 patients) and other therapy (three patients). In the pre-DFS setting, 19 patients received alternative systemic therapy, including a checkpoint inhibitor (18 patients), chemotherapy (six patients) and ADCs (one patient).

In the Keytruda arm, 48.4% of patients experienced side effects of grade 3 or higher, meaning that they were moderate to severe. In total, 38.6%, 4.9% and 4.9% of patients had grade 3 (moderate), 4 (severe) and 5 (fatal) side effects, respectively. Grade 3 and 4 blood-related side effects were observed in 5.5% and 0.9% of patients, respectively. Among the non-hematologic side effects observed, 37.7%, 4.6% and 4.9% were grade 3, 4 and 5, respectively.

Keytruda Side Effects: ‘If Something Doesn’t Feel Right … Call’

In the observation arm, 31.8% of patients experienced side effects of grade 3 or higher. In total, 23.3%, 3.8% and 4.7% of patients had grade 3, 4 and 5 side effects, respectively. Grade 3 blood-related side effects were observed in 2.6% of patients, and no grade 4/5 blood-related side effects were reported. Among the non-hematologic side effects observed, 22.7%, 3.8% and 4.7% were grade 3, 4 and 5, respectively.

Among the patients who received Keytruda, the most common treatment-related side effects were fatigue (any-grade, 47%; grade 3, 2%); itching (22%; 1%); diarrhea (21%; 3%); hypothyroidism (20%; 0%); maculo-papular rash (17%; 2%); increased creatine (15%; 1%); anorexia (15%; 1%); anemia (14%; 2%); increased lipase, which can indicate pancreatic issues (13%; 3%); difficulty breathing (11%; 0%); increased serum amylase, which can also indicate pancreatic issues (9%, 2%); hyperthyroidism (8%; 0%); and increased alanine aminotransferase (6%; 1%). Additionally, 1% of patients experienced grade 4 lipase increase.

“These results support adjuvant (Keytruda) as a new therapeutic option for patients MIUC at high risk of recurrence,” Apolo concluded.

Follow-up is ongoing for the final DFS/OS analysis of AMBASSADOR, as well as the ctDNA analyses and additional correlative analyses.

Postsurgical Keytruda improved disease-free survival — but not overall survival — in patients with locally advanced, muscle-invasive bladder cancer. 

Ashling Wahner

Darzalex Regimen Boosts Rates of MRD Negativity in Newly Diagnosed, Transplant-Eligible Myeloma

Conjugated Equine Estrogen Increases Gynecologic Cancer Death Rates

Orca-T Improves Post-Transplant Survival in Patients With Blood Cancers

Keytruda Improves Disease-Free Survival in Advanced Bladder Cancer

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