Jurnal Internasional Induksi bebas kemoterapi di MCL: siap untuk prime time?
Early treatment of MCL represents a unique challenge for doctors, given that there is no standard first-line therapy. Despite improvements in survival with the current treatment approach, MCL remains incurable. Selection of treatment for individuals considers patient factors such as age and comorbidity and lymphoma features, including the level of disease burden and disease biology. The most commonly used induction approaches including chemoimmunotherapy are often followed by consolidation with autologous stem cell transplantation and / or maintenance of rituximab, which has shown the greatest impact on the duration of remission. This intensive approach is related to treatment-related toxicity which makes them intolerable in patients with impaired organ function, poor performance status, or advanced age in diseases where the median age at diagnosis is 65 years. Determination of first-line regimens that extend disease remission and minimize unacceptable toxicity remains a priority, especially in patients not considered candidates for aggressive treatment or those with high-risk disease features who have lower outcomes despite aggressive treatment. Ruan et al designed this phase 2 study of lenalidomide and rituximab (LR) as an alternative regimen with standard chemoimmunotherapy in patients with untreated MCL.
Ruan et al 2 previously reported transient results from their multicenter. Phase 2 trials on MCL that were not treated with LR induction were followed by LR maintenance. This study involved 38 patients in 4 locations. At a median of 30 months follow-up, the LR combination had a 92% overall response rate (ORR) and 64% complete response (CR) level in 36 patients who could be evaluated. Median development-free survival (PFS) is not achieved; 2-year PFS is 85% and 2-year overall survival (OS) is 97%. Independent responses to features of high-risk diseases, including the MCL International Prognostic Index and Ki-67 proliferation index. These results were impressive in the context of the median PFS reported with standard chemoimmunotherapy regimens in a comparable patient population, 3 4 which provided reasons for further development of non-traditional induction regimens. However, the resistance of the regimen remains uncertain.
In the article by Ruan et al in this problem, the authors provide long-term data on the combination of LR. With an average follow-up of 64 months, LR continued to be well tolerated, and reported side effects occurred with less frequency and severity in the maintenance phase than previously reported by induction. Median PFS is not reached. Three-year PFS is estimated to reach 80.3% and 5-year PFS is estimated to reach 63.9%; OS 3 years is 89.5% and OS 5 years is 77.4%. Although this combination treatment has not been studied prospectively, the authors were able to show that it produced minimal negative disease in a subset of patients who achieved CR.
Some new target therapies have proven to be very effective in relapsing / refractory MCL, which leads to Food and Drug Administration Approval US (FDA), including oral tyrosine kinase inhibitors Bruton ibrutinib 5 6 proteasome inhibitors bortezomib, 7 and oral immunomodulatory agents lenalidomide. 8 9 Lenalidomide received FDA approval based on studies showing activity in this patient population, with the largest study having ORR 35% 8 when used as a single agent therapy, which increased to 57% when used in combination with rituximab. 9
The efficacy and safety of this therapy in relapsing MCL have resulted in prioritizing the incorporation of these agents into the initial therapeutic regimen, including induction and maintenance strategies. Although several clinical trials are investigating these agents in combination with standard chemoimmunotherapies (1945929) NCT02427620 NCT02427620 NCT01415752 NCT01776840 NCT01972840 and EudraCT Number 2012-002542-20), Ruan et al presented long-term follow-up data on the induction and maintenance regimen of the first nonchemotherapy maintenance for MCL. Although only 38 patients were treated, 5-year CHD from this regimen was important when considering that some chemotherapy regimens were more intensive, 10 which increased the likelihood that aggressive chemotherapy might not be the optimal approach in all patients, despite their ability to tolerate this therapy. Phase 2 of the ongoing LR trial in combination with ibrutinib ( NCT03232307 can further improve the effectiveness and resistance of this regimen, but the costs for toxicity remain to be seen. In the end, randomized research and a large number of treated patients will be needed before universally adapting a completely chemotherapy-free approach to MCL in first-line settings. However, in diseases that cannot be cured with standard therapy, the success of this regimen should not depend on their ability to achieve superior efficacy for chemotherapy but must depend on their ability to provide alternative effective therapies that are well tolerated in most patients.
Disclosure of conflict of interest: KM has received research funding from Farmaklik, Bristol-Myers Squibb, Merck, and Novartis and has consulted for Pharmacyclic, Janssen, Astra Zeneca, Genentech, Bristol-Myers Squibb, Teva , Novartis, Bayer, and Seattle Genetics.
- Submitted 24 September 2018.
- Received September 27 2018.
- © 2018 by The American Society of Hematology