scholarly journals Indirect comparison of tisagenlecleucel and blinatumomab in pediatric relapsed/refractory acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Michael R Verneris ◽  
Qiufei Ma ◽  
Jie Zhang ◽  
Amy K Keating ◽  
Ranjan Tiwari ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Propensity Score ◽  
Lymphoblastic Leukemia ◽  
Indirect Comparison ◽  
Patient Characteristics ◽  
Treatment Comparison ◽  
Real World Evidence ◽  
Level Data ◽  
Lower Hazard

In the absence of head-to-head trials, an indirect-treatment comparison can estimate the treatment effect of tisagenlecleucel in comparison with blinatumomab on rates of complete remission (CR) and overall survival (OS) in patients with relapsed or primary refractory (R/R) acute lymphoblastic leukemia (ALL). Patient-level data from two pivotal trials, ELIANA (tisagenlecleucel; n = 79) and MT103-205 (blinatumomab; n = 70), were used in comparisons of CR and OS, controlling for cross-trial difference in available patient characteristics. Five different adjustment approaches were implemented: stabilized inverse probability of treatment weight (sIPTW); trimmed sIPTW; stratification by propensity score quintiles; adjustment for prognostic factors; and adjustment for both prognostic factors and propensity score. Comparative analyses indicate that treatment with tisagenlecleucel was associated with a statistically significant higher likelihood of achieving CR and lower hazard of death than treatment with blinatumomab. The tisagenlecleucel group exhibited a higher likelihood of CR than the blinatumomab group in every analysis regardless of adjustment approach (odds ratios: 6.71-9.76). Tisagenlecleucel was also associated with a lower hazard of death than blinatumomab in every analysis, ranging from 68% to 74% lower hazard of death than with blinatumomab, determined using multiple adjustment approaches (hazard ratios: 0.26-0.32). These findings support the growing body of clinical trial and real-world evidence demonstrating that tisagenlecleucel is an important treatment option for children and young adults with R/R ALL.

VP90 Which Matching Adjusted Indirect Comparison Method Is Best?

2019 ◽  
Vol 35 (S1) ◽  
pp. 94-95
Author(s):  
Jonathan Alsop ◽  
Lawrence Pont ◽  
Martin Scott
Keyword(s):  
Treatment Effectiveness ◽  
Indirect Comparison ◽  
Patient Characteristics ◽  
Comparison Method ◽  
Ease Of Use ◽  
Superior Performance ◽  
Weighting Method ◽  
Entropy Balancing ◽  
Level Data ◽  
Adjusted Indirect Comparison

IntroductionMatching adjusted indirect comparison (MAIC) methods are extremely useful when conducting ITCs, as they reduce baseline imbalances between studies, particularly upon patient characteristics that are confounded with treatment. The standard approach when conducting MAIC is that proposed by Signorovitch et al. (2010). However, there are newer, and potentially better, methods available.MethodsThree different MAIC methods (Signorovitch, Entropy Balancing, Polynomial Weighting) were compared using multiple phase 3 RCTs conducted in Diabetic Retinal Edema. The matching ability of each method was assessed, alongside its ability to avoid large weights (i.e. avoiding high leverage), and maximise effective same size (ESS). Each method's overall ease of use and impact upon estimates of treatment effectiveness were also evaluated.ResultsAll methods were able to precisely match the aggregate level data. However, the Entropy Balancing and Polynomial Weighting both outperformed the Signorovitch method in terms of having the lowest maximum weights. The Polynomial Weighting provided the highest ESS. The Entropy Balancing method was arguably the most challenging to implement, whilst the Signorovitch method the least. The Polynomial Weighting method appears to provide the greatest flexibility to the user.ConclusionsWhilst the Signorovitch method has become almost synonymous with MAIC, the Entropy Balancing and Polynomial Weighting methods offer potentially superior performance. In the absence of head-to-head trial data, these new MAIC approaches should provide less biased and more precise estimates of comparative effectiveness – ultimately leading to better decision making by regulators and payers.

A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969.

1988 ◽  
Vol 6 (6) ◽  
pp. 1014-1030 ◽  
Author(s):  
J Gaynor ◽  
D Chapman ◽  
C Little ◽  
S McKenzie ◽  
W Miller ◽  
...  
Keyword(s):  
Weight Loss ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Hazard Rate ◽  
Lymphoblastic Leukemia ◽  
Performance Status ◽  
Factors Associated ◽  
Rate Analysis ◽  
Resistant Disease ◽  
Cause Specific Hazard Rate

Results of a multivariable analysis of prognostic factors are reported for 199 previously untreated adults with acute lymphoblastic leukemia (ALL). These patients have long-term follow-up, and the probability of cure is estimated at approximately 35%. The cause-specific hazard rate analysis found lower rates of achieving complete remission (CR) in patients with WBC greater than 10,000/microL, AUL (undifferentiated) morphology, and older age. Since these patients required additional time to respond, fewer of them actually achieved CR. Characteristics directly associated with a higher rate of death during induction therapy due to severe bone marrow suppression were low serum albumin concentration (less than or equal to 3.5 g/dL), age greater than 50 years, acute undifferentiated leukemia (AUL) morphology, low Karnofsky performance status, and weight loss greater than 5%. Factors associated with a higher rate of relapse were WBC greater than 20,000/microL, non-T cell ALL, age greater than 60 years, Ph' + ALL, and time to achieve CR greater than 5 weeks. These criteria were used to identify patients at high risk of relapse. In addition, the predictive value of high WBC was found to disappear by 18 months of continuous CR. Finally, the rate of death following first relapse was higher in patients with a short first remission duration, high percentage weight loss at initial diagnosis, and older age. In summary, factors associated with a higher rate of death during attempted induction (ie, low albumin, high percent weight loss, and poor performance status) had no association with the patient's ability to remain relapse-free. Conversely, factors correlating with more extensive or resistant disease (ie, high WBC, null or B cell ALL, or Ph' + ALL) showed no association with the ability to tolerate therapy. Thus, a less toxic but more effective induction regimen is needed for patients with a poor clinical status, whereas a more intensive form of therapy appears warranted for patients presenting with more extensive or resistant disease.

Treatment Outcome and Prognostic Factors for Infants With Acute Lymphoblastic Leukemia Treated on Two Consecutive Trials of the Children's Cancer Group

1999 ◽  
Vol 17 (2) ◽  
pp. 445-445 ◽  
Author(s):  
Gregory H. Reaman ◽  
Richard Sposto ◽  
Martha G. Sensel ◽  
Beverly J. Lange ◽  
James H. Feusner ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Historical Controls

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (> 95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG-1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG-1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/μL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG-1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

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