scholarly journals Safety and Efficacy of Purine Analogs for Treatment of Waldenstrom Macroglobulinemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Abdul Jabbar Dar ◽  
Qasim Khurshid ◽  
Muhaddis Ejaz Ahmad ◽  
Muhammad Ali Mirza ◽  
Farhan Khalid ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
The United States ◽  
Cochrane Library ◽  
Waldenström Macroglobulinemia ◽  
Overall Response ◽  
Waldenstrom Macroglobulinemia ◽  
Purine Analogs ◽  
Number Of Patients

Introduction: There are about 1500 cases every year in the United States of America and while the disease is incurable but it is treatable. Purine analogs are anti-metabolites that mimic the structure of metabolic purines and are used for the treatment of Waldenstrom macroglobulinemia (WM). Methods: We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after 1995, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library and Web of Science. Total 580 articles were identified initially and after detailed screening, we finalized 16 studies involving patients with Waldenstrom macroglobulinemia. Results: The total number of patients in the studies involving regimens based on purine analogs were 1211. The doses of Fludarabine ranged from 25-30 mg/m2 and that of Cladribine ranged from 0.1-0.5 mg/kg. The complete response (CR) observed ranged from 2-15% and the partial response (PR) ranged from 11-67%. The overall response rate (ORR) ranged from 38-95%. Fludarabine: In the study Dhodapkar et al., N=231, the highest CR and ORR was observed, 4% and 66% respectively. In the study Zinzani et al., the PR was 41%. Fludarabine and Cyclophasphamide: In the study Dimopoulos et al., the PR was 55% and the progression free survival (PFS) was 24 months. Fludarabine, Cyclophosphamide and ofatumumab: In the study Gavriatopoulou et al., the PR was 67% and very good partial response (VGPR) was 17% and the PFS was 23 months. Fludarabine, rituximab and cyclophosphamide: In the study Tedeschi et al., the CR was 11.60%, ORR was 79% and the PR was 41.8%. Fludarabine and Rituximab: In the study Treon et al., the CR was 4.6%, VGPR was 32.5%, PR was 48%, and ORR was 95.3% with PFS of 51.2 months. Cladribine: In the study Liu et al., the CR was 5% and PR was 50%. In the studies Dimopoulos et al., 1994 the highest CR was observed, 11.5% with an ORR of 85%. The PR was also the highest, 73%. Conclusion: There is limited literature on regimens containing both Fludarabine and Cladribine, which are used for the treatment of WM. Despite heterogenicity in WM patients and various regimens used in literature. Purine analogs containing regimens are a remarkably effective treatment with overall response rates reaching up to 79%. Neutropenia and thrombocytopenia were the main side effects. There is a paucity of phase 3 randomized trials demonstrating a clinical benefit of anyone regimen over another. We recommend future randomized prospective trials better to understand the efficacy and safety profile of regimens containing purine analogs. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

scholarly journals A Systemic Review on Efficacy of Ibrutinib-Based Regimens for the Treatment of Waldenstrom Macroglobulinemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-9
Author(s):  
Qasim Khurshid ◽  
Abdul Jabbar Dar ◽  
Muhammad Ali Mirza ◽  
Muhaddis Ejaz Ahmad ◽  
Ali Jaan ◽  
...  
Keyword(s):  
Partial Response ◽  
Overall Response Rate ◽  
Response Rate ◽  
Systemic Review ◽  
Cochrane Library ◽  
Progression Rate ◽  
Waldenström Macroglobulinemia ◽  
Overall Response ◽  
Waldenstrom Macroglobulinemia ◽  
Number Of Patients

Introduction: Ibrutinib works by inhibiting downstream signaling after the interaction between the mutated MYD88 (Leu265Pro) protein and BTK. In 2015, Ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK), was approved by the U.S Food and Drug Administration (FDA) for patients with symptomatic Waldenstrom Macroglobulinemia (WM). Methods: We performed a comprehensive literature search following PRISMA guidelines. Beginning with articles published after April 2015, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library, and Web of Science. A total of 580 articles were identified initially, and after a detailed screening, we finalized 4 studies involving 248 WM patients. Results: The total number of patients who received Ibratunib based regimens were 248. The dose ranged from 140-560 mg. The overall response rate ranged from 90-92%, very good partial response ranged from 13-23%, and the partial response ranged from 36-75%. 1) Ibtrutunib +Rituximab: In a study by Dimopoulos et al., (N=150), the overall response rate (ORR) was 92% vs 47% in control vs placebo respectively. The progression-free survival (PFS) of 30 months was 82% vs 28% respectively. 2) Ibrutinib alone: In a study by Dimopoulos et al., with (N=31), ORR was 90%, a very good progression rate (VGPR) was 13 %, and the partial response (PR) was 58%. In a study by Treon et al., (N=63) ORR was observed in Treon et al. at 90.50%, VGPR was 15%, PR was 36%, no response (NR) was 57%, with overall survival (OS) was 24 months. In a study by Richard et al., (N=4), PR was noted at 75%. Conclusion: Ibtrutunib used for the treatment of WM showed an overall response rate of 92%. Infections, cytopenia, bleeding, hypertension and atrial fibrillation were major side effects reported. However, due to the recent FDA approval of the drug to be used for the patients of WM there is very limited studies on Ibrutinib. We recommend future randomized prospective trials to understand the efficacy and safety profile of Ibrutinib for WM treatment. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom macroglobulinemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8043-8043
Author(s):  
Irene M. Ghobrial ◽  
Morie A. Gertz ◽  
Betsy LaPlant ◽  
John Kelly Camoriano ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Long Term Results ◽  
Entire Study ◽  
Waldenström Macroglobulinemia ◽  
Overall Response ◽  
Waldenstrom Macroglobulinemia

8043 Background: The mammalian target of rapamycin (mTOR) signal pathway controls cell proliferation and survival. The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus (TORC1 inhibitor) in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Methods: Eligible patients had measurable disease (IgM monoclonal protein >1000 mg/dL with >10% marrow involvement or nodal masses >2 cm), a platelet count ≥75,000 x 106/L, a neutrophil count ≥1,000 x 106/L. Patients received everolimus 10 mg PO daily. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 60 pts were treated. The median age was 64 years (range, 43-85). The median number of prior therapies was 3 (range, 1-11). All but two patients (97%) had received prior rituximab based therapy and 64% of patients had received prior alkylator based therapies. The overall response rate (complete response CR+ partial response PR+ minimal response MR) was 73% (95% CI: 60-84%), with a PR of 50% and 23% MR. The median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) for the entire study population is 28 months (mos), (95% CI: 18-not reached (NR)), 22 mos (95% CI: 12 0-NR), and 55 mos (95% CI: 55-NR), respectively. The estimated PFS at 12 and 24 months is 62% (95%CI: 51-75%), and 48% (95%CI: 37-63%), respectively. The 30 patients who achieved a PR responded after a median of 2 months (range, 1-26) of treatment. The median duration of response (DR) for these patients has not yet been reached and 19 of these patients remain in response after a median follow up of 31 months (range, 3-54). All but two patients had a decrease in their serum IgM. Grade 3 or higher related toxicities were observed in 67% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 5% of patients. Dose reductions due to toxicity occurred in 63% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 73% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient population.

A Systematic Review on Efficacy and Safety of Bortezomib Based Regimens for Treatment of Waldensterom Macroglobulinemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Abdul Jabbar Dar ◽  
Qasim Khurshid ◽  
Muhaddis Ejaz Ahmad ◽  
Muhammad Ali Mirza ◽  
Farhan Khalid ◽  
...  
Keyword(s):  
Partial Response ◽  
Response Rate ◽  
Immunoglobulin M ◽  
Cochrane Library ◽  
Published Data ◽  
Efficacy And Safety ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Major Response ◽  
Number Of Patients

Introduction: Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration and immunoglobulin M (IgM) monoclonal gammopathy. Various studies have shown that the proteasome inhibitor bortezomib (V) targets signaling pathways of relevance in WM. We reported published data on the efficacy profile of (V) for the patients of WM. Methods: We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after 2004, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library and Web of Science. Total 580 articles were identified initially and after detailed screening, we finalized 9 studies involving 375 patients with Waldenstrom Macroglobulinemia (WM) treated by combination of Bortezomib. Results: The total number of patients in the studies involving Bortezomib were 375 and dose of the drug used ranged between 1.3 mg/m2 to 1.6mg/m2. The Complete response (CR) ranged from 0-19% and the partial response (PR) ranged from 44-58%. Bortezomib(V): In the study Treonet et al., N=27, the highest major respose rate was 85% and minimal response rate was 37%. In the study Chen et al., N=27, the major response rate was 26% and the PR was 44%. Progression free survival (PFS) was 16.3 months for Chen et al. Bortezomib(V), Rituximab(R), and Dexamethasone(D): In the study Treon et al., N=23, the highest major response rate was 96%, CR was 13%, Very good partial response (VGPR) was 13%, and PR was 46%. Highest PR and was observed in Dimopolous et al., which was 58% and 42 months respectively. Bortezomib(V), and Rituximab(R): In the study Agathocleus et al., N=42, the highest CR was 14.2-19%. The highest PR was between 47.6-52.3%. In the study Ghobrial et al., N=37, the CR was 3% and PR was 46%. PFS was 15.6 months. Bortezomib(V), Rituximab(R) and Everolimus(E): In the study Ghobrial et al., N=46, the CR was 4%, PR was 46% and PFS was 18 months. Conclusion: Despite heterogenicity in WM patients and various regimens used in literature, Bortezomib containing regimens are a remarkably effective treatment. Combination regimens showed an overall response rate of 96%. The main side effects being anemia, leukopenia, thrombocytopenia, nausea and sensory neuropathies. Although we recommend future randomized prospective trials to better understand the efficacy and safety profile of Bortezomib for WM treatment. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

scholarly journals Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial

2020 ◽  
Vol 4 (23) ◽  
pp. 6009-6018
Author(s):  
Meletios Dimopoulos ◽  
Ramon Garcia Sanz ◽  
Hui-Peng Lee ◽  
Marek Trneny ◽  
Marzia Varettoni ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Waldenström Macroglobulinemia ◽  
Activating Mutations ◽  
Waldenstrom Macroglobulinemia ◽  
Mutational Status ◽  
Major Response ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Poor Outcomes

Abstract Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.

scholarly journals CXCR4 S338X clonality is an important determinant of ibrutinib outcomes in patients with Waldenström macroglobulinemia

2019 ◽  
Vol 3 (19) ◽  
pp. 2800-2803 ◽  
Author(s):  
Joshua N. Gustine ◽  
Lian Xu ◽  
Nicholas Tsakmaklis ◽  
Maria G. Demos ◽  
Amanda Kofides ◽  
...  
Keyword(s):  
Partial Response ◽  
Important Determinant ◽  
Progression Free Survival ◽  
Free Survival ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Key Points ◽  
Clonality Assessment ◽  
Good Partial Response

Key Points CXCR4 S338X clonality ≥25% is associated with lower very good partial response and shorter progression-free survival to ibrutinib. CXCR4 S338X clonality assessment represents a novel biomarker to predict outcomes to ibrutinib in Waldenström macroglobulinemia patients.

scholarly journals Predictors of response and survival in a large cohort of 319 Waldenström macroglobulinemia patients treated with ibrutinib monotherapy

2021 ◽  
Author(s):  
Jorge J. Castillo ◽  
Shayna Sarosiek ◽  
Joshua N Gustine ◽  
Catherine Flynn ◽  
Carly Leventoff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Partial Response ◽  
Multiple Imputation ◽  
Progression Free Survival ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Predictors Of Response ◽  
Two Factors ◽  
Cox Proportional Hazard Regression ◽  
Btk Inhibitors

Bruton tyrosine kinase (BTK) inhibitors are the only FDA-approved treatments for Waldenström macroglobulinemia (WM). Factors prognostic of survival and predictive of response to BTK inhibitors remained to be clarified. We evaluated 319 patients with WM to identify predictive and prognostic factors on ibrutinib monotherapy. Logistic and Cox proportional-hazard regression models were fitted for response and survival. Multiple imputation analyses were used to address bias associated with missing data. Major (partial response or better) and deep responses (very good partial response or better) were attained in 78% and 28% of patients. CXCR4 mutations were associated with lower odds of major (OR 0.2, 95% CI 0.1-0.5; p<0.001) and deep response (OR 0.3, 95% CI 0.2-0.6; p=0.001). CXCR4 mutations (HR 2.0, 95% CI 1.2-3.4; p=0.01) and platelet count 100 K/uL or less (HR 2.5, 95% CI 1.3-4.9; p=0.007) were associated with worse progression-free survival (PFS). We proposed a scoring system using these two factors. The median PFS for patients with zero, one and two risk factors were not reached, 5 years and 3 years (p<0.001). Patients with two risk factors had HR 2.2 (95% CI 1.3-3.8; p=0.004) compared with one factor, and patients with one factor had HR 2.3 (95% CI 1.1-5.1; p=0.03) compared with zero factors. Age 65 years or older was the only factor associated with overall survival (HR 3.2, 95% CI 1.4-7.0; p=0.005). Multiple imputation analyses did not alter our results. Our study confirms the predictive and prognostic value of CXCR4 mutations in patients with WM treated with ibrutinib monotherapy.

scholarly journals A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study

Blood ◽  
2020 ◽  
Vol 136 (18) ◽  
pp. 2038-2050 ◽  
Author(s):  
Constantine S. Tam ◽  
Stephen Opat ◽  
Shirley D'Sa ◽  
Wojciech Jurczak ◽  
Hui-Peng Lee ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Phase 3 ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Major Response ◽  
Significant Difference ◽  
Duration Of Response ◽  
Btk Inhibitor ◽  
Grade 3

Abstract Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

Bortezomib plus Dexamethasone versus Fludarabine plus Cyclophosphamide in initial treatment of patients with Waldenström macroglobulinemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5107-5107
Author(s):  
Yaping Zhang ◽  
Zenghua Lin ◽  
Xinfeng Wang ◽  
Xin Cao ◽  
Guoqi Song ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Peripheral Neuropathy ◽  
Initial Treatment ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Complete Response ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Group A ◽  
Grade 3

Abstract Purpose We examined the efficacy of bortezomib plus dexamethasone(BD) versus fludarabine plus cyclophosphamide(FC) in patients with symptomatic, untreated Waldenström macroglobulinemia(WM). Furthermore, to evaluate the toxicity of BD regimen in WM. Patients and methods: 17 untreated WM patients received either bortezomib and dexamethasone(n=7) or fludarabine and cyclophosphamide(n=10). BD group: A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11. Patients received 4 cycles at least. FC group: A cycle of therapy consisted of fludarabine 25 mg/m2 on days 1-3; cyclophosphamide 250mg/m2 on days 1-3. Patients received 4-6 consecutive cycles for induction therapy. Responses were based on paraprotein levels. Herpes zoster prophylaxis was instituted with using oral valacyclovir. Results: In BD and FC groups, the overall response rates(PR+MR) were 86% versus 70% respectively. There was not complete response in two groups. In BD and FC groups, minor and partial responses occurred at a median of 25 vs. 54 days and 55 vs. 94 days respectively(P<0.05, respectively). The median progression-free survival(PFS) was 27 months, and a median follow-up of 62 months the actuarial 5-year overall survival(OS) rate was 80% in FC group. Because of a short following time, there were not PFS and OS that can be observed in BD group. Hemoglobin and platelet levels increased normally in 83% vs. 50% and 100% vs. 66% patients in BD and FC groups respectively(P<0.05, respectively). In BD group, peripheral neuropathy was the most common toxicity(57% grade 1- 2, no grade 3- 4). Hematologic toxicities included grade 3 to 4 thrombocytopenia in 2/7(28%) and neutropenia in 1/7(14%). 42% patients developed herpes zoster. Conclusions: The results demonstrate that BD produces rapid responses, along with high rates of response in WM, and it was generally well-tolerated in our study. Herpes zoster prophylaxis is necessary with BD, and peripheral neuropathy was the most common toxicity, but not leading to discontinuance of BD. This retrospective analysis confirms that BD therapy is an effective initial treatment in WM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098054
Author(s):  
Huilin Xu ◽  
Ximing Xu ◽  
Wei Ge ◽  
Jinju Lei ◽  
Dedong Cao
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Good Survival ◽  
Solid Cancer ◽  
Cancer Type ◽  
Early Effect ◽  
Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

Sign in / Sign up

Export Citation Format

Share Document