Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group

Ribera, Josep‐Marǐa; García, Olga; Oriol, Albert; Gil, Cristina; Montesinos, Pau; Bernal, Teresa; González‐Campos, José; Lavilla, Esperanza; Ribera, Jordi; Brunet, Salut; Martínez, M. Labalde; Tormo, Mar; Genescà, Eulàlia; Barba, Pere; Sarrà, Josep; Monteserin, M. C.; Soria, Beatriz Yolanda Moratilla; Colorado, Mercedes; Cladera, Antònia; García‐Guiñón, Antoni; Calbacho, M.; Serrano, Alfons; Ortı́n, Xavier; Pedreño, María; Amigo, María‐Luz; Escoda, Lourdes; Feliú, Evarist

doi:10.1016/j.leukres.2015.11.012

Cited by 46 publications

(33 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High remission rates were observed (87%) and median survival was 37.3 months. 16 The question as to whether dasatinib improves the prognosis of Ph For personal use only. on May 12, 2018.…”

Section: Discussionmentioning

confidence: 99%

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL

Rousselot

Coude

Gökbuget

et al. 2016

Blood

252

197

View full text Add to dashboard Cite

Key Points• Dasatinib, combined with lowintensity chemotherapy, gave 36% 5-year overall survival in Ph 1 ALL patients older than age 55 years.• Prospective monitoring of mutations may be useful to personalize therapy in Ph 1 ALL patients not eligible for intensive therapies. Prognosis of Philadelphia-positive (Ph 1) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph + ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1T315I was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph 1 ALL. Monitoring of BCR-ABL1 T315I from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy. (Blood. 2016;128(6):774-782)

show abstract

“…High remission rates were observed (87%) and median survival was 37.3 months. 16 The question as to whether dasatinib improves the prognosis of Ph For personal use only. on May 12, 2018.…”

Section: Discussionmentioning

confidence: 99%

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL

Rousselot

Coude

Gökbuget

et al. 2016

Blood

252

197

View full text Add to dashboard Cite

show abstract

“…Advancements in treating older adults with Ph þ ALL and the utilization of RIC allogeneic HCT in older adults were discussed earlier; here we note that subtype-oriented therapy is feasible in elderly patients with ALL and resulted in improving outcomes among those with Ph þ ALL compared to those with Ph À ALL [88], mainly because of the introduction of TKIs. Studies have shown that older adults do not tolerate intensive conventional ALL regimens well, with high risk of treatment-related mortality (TRM) [89,90].…”

Section: All In Older Adultsmentioning

confidence: 70%

Advances in adult acute lymphoblastic leukemia therapy

Aldoss

Stein

2017

Leukemia & Lymphoma

View full text Add to dashboard Cite

Progress in adult acute lymphoblastic leukemia (ALL) treatment has been met with challenge until recently. A steady improvement in outcomes is being witnessed among adults with ALL, and it will be enhanced further with early referral of newly diagnosed ALL patients to specialized centers, enrolling more ALL adults in clinical trials, adopting pediatric-inspired ALL regimens in younger adults, tailoring treatments according to minimal residual disease response and disease genetics, incorporating novel therapies and tyrosine kinase inhibitors in frontline regimens, early referral to transplant when indicated, expanding the donor pool, and developing more effective salvage therapies for relapsed/refractory ALL. In this review, we will discuss the most significant advances in treating adult ALL observed in the last five years that have the potential to enhance adult ALL treatment and outcome.

show abstract

“…Therefore induction therapy is the most critical phase for management. In older patients, induction mortality has a wide range (0% to 42%) (Table 2), 14,[16][17][18][19][20][21][22][23][24][25] and early death occurs also before the onset of chemotherapy. The most frequent cause of death in induction is infection.…”

Section: Induction Therapymentioning

confidence: 99%

“…The authors also observed grade 3-4 infections in 62% of the patients during induction therapy with a median duration of neutropenia of 24 days, whereas consolidation was far better tolerated even when including the use of asparaginase. 22 The GMALL has conducted thus far the largest prospective trial specifically designed for older patients with Ph/BCR-ABLnegative ALL. Pediatric (Berlin-Frankfurt Munster)-based, dosereduced induction therapy with idarubicin, dexamethasone, vincristine, cyclophosphamide, and cytarabine was followed by alternating consolidation cycles for 1 year and maintenance.…”

Section: Prospective Studies For Older All Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of older patients with acute lymphoblastic leukemia

Gökbuget

2016

Hematology

View full text Add to dashboard Cite

The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients. Some progress has been made with delivering age-adapted, moderately intensive chemotherapy protocols for Ph/BCR–ABL-negative ALL and combinations of tyrosine kinase inhibitors with chemotherapy in Ph/BCR–ABL-positive ALL. For the future, optimizing supportive care, introducing targeted therapies, novel immunotherapies, moderately intensified consolidation strategies, and reduced intensity SCT are promising approaches. Prospective clinical trials for older patients are urgently needed to test these approaches.

show abstract

Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group

Cited by 46 publications

References 40 publications

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL

Advances in adult acute lymphoblastic leukemia therapy

Treatment of older patients with acute lymphoblastic leukemia

Contact Info

Product

Resources

About