Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia

Jabbour, Elias; Pui, Ching Hon; Kantarjian, Hagop M.

doi:10.1001/jamaoncol.2018.1915

Cited by 83 publications

(83 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All key patient subgroups appeared to benefit from InO, and patient selection for therapy might, therefore, be focused instead on avoiding risk for VOD. On the basis of these results, the next rational step would be combining InO with chemotherapy, and pilot studies using such combinations in salvage and elderly frontline ALL are already showing promise …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study

Kantarjian

DeAngelo

Stelljes

et al. 2019

Cancer

Self Cite

256

206

View full text Add to dashboard Cite

Background Inotuzumab ozogamicin (InO) is an antibody‐drug conjugate used for adults with relapsed/refractory B‐cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO‐VATE) previously reported improved outcomes with InO versus standard‐of‐care (SoC) chemotherapy. This article reports the final INO‐VATE results (≥2 years of follow‐up) and additional analyses of patient characteristics associated with improved outcomes. Methods Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open‐label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm). Results The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1‐sided P < .0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2‐year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57‐0.99; 1‐sided P = .0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow‐up hematopoietic stem cell transplantation (HSCT; all 2‐sided P values < .05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow‐up induction therapy (39.6% [95% CI, 32.1%‐47.6%] vs 10.5% [6.2%‐16.3%]; 1‐sided P < .0001). The most frequent all‐grade and grade 3 or higher adverse events in both arms were hematologic. Veno‐occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]). Conclusions In patients with relapsed/refractory BCP ALL in INO‐VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.

show abstract

Section: Discussionmentioning

confidence: 99%

“…On the basis of these results, the next rational step would be combining InO with chemotherapy, and pilot studies using such combinations in salvage and elderly frontline ALL are already showing promise. 21,22 FUNDING SUPPORT This study was sponsored by Pfizer, Inc.…”

Section: Discussionmentioning

confidence: 99%

Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study

Kantarjian

DeAngelo

Stelljes

et al. 2019

Cancer

Self Cite

256

206

View full text Add to dashboard Cite

show abstract

“…Current treatment approaches for adult ALL result in long-term survival for approximately 50% to 60% of patients. [1][2][3][4][5][6][7][8][9][10][11][12] This success rate is not paralleled in older patients, for whom the 5-year survival rate remains dismal (approximately 20%). [13][14][15][16][17] Li and colleagues recently reported a median survival of 10 months among 727 older patients (aged >65 years) who were diagnosed Cancer August 1, 2019 between 2007 and 2012 and treated under Medicare.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12] Similar intensive chemotherapy strategies have not yielded comparable results in older patients with ALL, who have estimated cure rates of only 10% to 20%. 1,2,[13][14][15][16][17] In older patients with ALL, intensive chemotherapy results in lower response rates than the rates observed in younger patients with ALL and in high rates of toxicities. [13][14][15] One-third of patients who achieve a complete response (CR) may die of myelosuppression-associated complications.…”

Section: Introductionmentioning

confidence: 99%

Inotuzumab ozogamicin in combination with low‐intensity chemotherapy (mini‐HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome‐negative acute lymphoblastic leukemia: A propensity score analysis

Jabbour

Sasaki

Ravandi

et al. 2019

Cancer

View full text Add to dashboard Cite

Background The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)‐negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low‐intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low‐intensity chemotherapy (mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini‐HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen. Methods The authors analyzed 135 older patients with newly diagnosed, Ph‐negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method. Results Propensity score matching identified 38 patients in each cohort. The antibody plus low‐intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3‐year event‐free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab were 34% and 64%, respectively (P = .003), and the 3‐year overall survival rates were 34% and 63%, respectively (P = .004). By multivariate analysis, age (P = .019; hazard ratio, 1.045) and the combination of inotuzumab plus mini‐HCVD with or without blinatumomab (P = .020; hazard ratio, 0.550) were identified as independent prognostic factors for survival. Conclusions The combination of inotuzumab ozogamicin plus mini‐HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph‐negative ALL and confers a better outcome compared with standard HCVAD chemotherapy.

show abstract

“…Adult (diagnosed at 20 years or older) acute lymphoblastic leukaemia (ALL) constitutes about 40% of ALL cases, 75% of which are B-cell lineage and 25% are T-cell lineage (Al Ustwani et al, 2016). Recurrent cytogenetic abnormalities are found in 70% of adults and 90% of children with ALL while the Philadelphia chromosome (BCR-ABL1 fusion) is far more common in adults (15-30%) than in children (2%) (Inaba et al, 2013;Al Ustwani et al, 2016;Jabbour et al, 2018). Other fusion genes are common in adult as well as childhood ALL (Inaba et al, 2013;Jabbour et al, 2018).…”

mentioning

confidence: 99%

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia

et al. 2019

View full text Add to dashboard Cite

Summary Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi‐directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non‐Hodgkin lymphoma and melanoma. The concordance between RRs for bi‐directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi‐directional risks with skin cancers and other immune‐related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

show abstract

Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia

Cited by 83 publications

References 81 publications

Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study

Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long‐term survival follow‐up from the randomized, phase 3 INO‐VATE study

Inotuzumab ozogamicin in combination with low‐intensity chemotherapy (mini‐HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome‐negative acute lymphoblastic leukemia: A propensity score analysis

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia

Contact Info

Product

Resources

About