Efficacy and Safety of Frontline Single-Agent Rituximab in Extranodal Marginal Zone Lymphoma.

First-line therapy for patients with extranodal marginal zone lymphoma (EMZL) is not well established, except for eradication therapy for Helicobacter pylori in early gastric MZL. Various regimens, for example, locoregional treatment and systemic chemo-immunotherapy, can be used depending on the site and stage of disease. Single-agent rituximab is a useful approach in the setting of localized, low-intermediate risk EMZL. The aim our research was to analyze the effectiveness and safety of single-agent rituximab (375 mg/m2 once weekly for 4 weeks) in naïve EMZL in a real-life setting. The primary endpoint was the overall response rate (ORR), secondary endpoints were progression-free (PFS), overall (OS) and disease-free survivals (DFS), and drug tolerability. Fifty-nine patients were analyzed. Median time between diagnosis and rituximab was 3.6 months. The ORR was 89.9%, with 67.8% complete response (CR). Median DFS and PFS were reached at 6.3 and 5.3 years, respectively. After a median follow-up of 5 years, median OS was not reached. The most common adverse event was infusion reaction, reported in 28 cases, mainly during the first infusion and easily manageable. Single-agent rituximab may represent a valid therapeutic option in the first-line treatment of EMZL, at least for localized disease, with a favorable toxicity profile.

A systematic literature review of clinical evidence and treatment burden in newly diagnosed high-risk pediatric patients with classical Hodgkin lymphoma.

This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n = 3115; full-text, n = 98) representing 12 studies (randomized controlled trials [RCTs], n = 2; non-comparative, non-randomized, n = 7; observational, n = 3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL.

The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Eltrombopag as frontline treatment of aplastic anaemia in routine practice: implications on cost and efficacy.

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.

Chidamide combined with cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with peripheral T-cell lymphoma.

OBJECTIVE: Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients. METHODS: This study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen. RESULTS: A total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2. CONCLUSIONS: The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

Real-world data on efficacy and safety of obinutuzumab plus chlorambucil, rituximab plus chlorambucil, and rituximab plus bendamustine in the frontline treatment of chronic lymphocytic leukemia: The GO-CLLEAR Study by the Czech CLL Study Group.

Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients.

Comparison of chemotherapy and chidamide combined with chemotherapy in patients with untreated angioimmunoblastic T-cell lymphoma.

Background: Angioimmunoblastic T-cell lymphoma (AITL) is characterized by high recurrence rates and poor prognosis, and effective first-line treatment is lacking. Recently, histone deacetylase inhibitors (HDACi), such as chidamide, have been found to induce durable remissions in AITL patients. Methods: Patients with untreated AITL from March 2015 to March 2023 were retrospectively collected and divided into chemotherapy (ChT) group and chidamide combined with chemotherapy (C-ChT) group based on the first-line treatment received. The comparison of efficacy and safety between the two groups was conducted. Results: 86 patients with newly diagnosed AITL were enrolled, in which 35 patients were in the ChT group and 51 in the C-ChT group. The objective response rate (ORR) of C-ChT group was significantly higher than that of ChT group (84.3% vs. 60%, P= 0.011), and had superior progression-free survival (PFS) (27 months vs. 12 months, P= 0.025). However, no significant difference in overall survival (OS) was observed between the two groups (P= 0.225). In addition, the responding patients who received autologous stem cell transplantation (ASCT) had superior PFS compared to those who did not (P= 0.015). Conclusions: Compared with ChT regimen, C-ChT regimen was well tolerated and had superior ORR and PFS in patients with untreated AITL. ASCT may contribute to longer PFS in remission patients.

Real-Life Multicenter Experience of Venetoclax in Combination with Hypomethylating Agents in Previously Untreated Adult Patients with Acute Myeloid Leukemia in Greece.

BACKGROUND: The landscape of first-line treatment for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy has changed remarkably after venetoclax approval. Accumulating real-world data further apprises us with more knowledgeable use. To assess the efficacy and safety challenges in the real-life setting of the combination of hypomethylated agent (HMA) and venetoclax, we conducted a multi-center retrospective study. METHODS: Forty adult AML patients treated with the combination of HMA and venetoclax as a first-line treatment after full approval (2020) were included. To confirm VIALE-A results, this group was compared to a historical cohort of 17 chemotherapy-ineligible AML patients treated with HMA monotherapy before 2020. RESULTS: The combination of HMA-venetoclax achieved a composite complete response rate of 86.8% (p < 0.001), median overall survival, and event-free survival of 33.8 and 19.7 months, respectively, in a median follow-up of 17.8 months (pos < 0.001, HR = 0.276, CI: 0.132-0.575, pEFS = 0.004, HR = 0.367, CI: 0.174-0.773). High rates of neutropenia (90%) and consequent infection rates (57.5%) were noted. Only 55% of our patients received antifungal prophylaxis, as its use remains controversial, and invasive fungal infections were presented in 7.5%. CONCLUSIONS: Evidently, venetoclax-HMA yields high response rates and profound survival benefits in real life and has changed our approach to alternative chemotherapy options.

Treatment attrition rates and relevant risk factors in multiple myeloma: A real-world study in China.

Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China. Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank" Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition. Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment. Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.

First-line treatment of multiple myeloma in both transplant and non-transplant candidates.

INTRODUCTION: The last decade's progress in the treatment of newly diagnosed multiple myeloma has relied on the synergistic combination of agents with different mechanisms of action, basically proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, in order to achieve the deepest possible response early in the course of treatment. Following induction, several therapeutic strategies aim to improve and maintain response. AREAS COVERED: The manuscript reviews available data for the treatment of newly diagnosed multiple myeloma patients with a focus on most recent induction and maintenance combinations and the still important role of autologous stem transplantation. Future perspectives in the light of initial results from ongoing clinical trials are also addressed. EXPERT OPINION: Remarkable progress has been made in myeloma treatment due to the integration of immunomodulators, proteasome inhibitors, monoclonal antibodies, and high dose therapy in the frontline setting. Upfront therapy may be further improved intensifying induction combinations, adapting high dose therapy and consolidation strategies to the patient's profile, improving maintenance in high-risk individuals, or limiting maintenance duration in those with a better prognosis. Evidence needs to be reviewed, taking into account the therapeutic objectives at each treatment stage and patient specific risk factors.

Frontline therapy for advanced hepatocellular carcinoma: an update.

Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer-related mortality in the United States and is projected to be the third leading cause of cancer-related mortality in the United States by 2030. Main risk factors include alcoholic cirrhosis, chronic hepatitis B, hepatitis C, and nonalcoholic steatohepatitis (NASH). More than half of the patients have advanced-stage disease at presentation. Currently approved frontline systemic therapy options include sorafenib, lenvatinib, and atezolizumab/bevacizumab. Over the past decade, there has been a significant improvement in survival with a median overall survival of 19.2 months reported with first-line treatment with atezolizumab/bevacizumab. Based on positive results of randomized phase III HIMALAYA trial, durvalumab and tremelimumab combination could become another frontline option. Multiple frontline clinical trials with immune checkpoint inhibitor (ICI) or ICI combined with other novel agents are underway. In the frontline setting, identifying predictive biomarkers for ICI-based or tyrosine kinase (TKI)-based therapy is an unmet need. Subsequent treatment is poorly defined in patients with prior ICI-based therapy since all the available second-line and beyond therapy was studied after first-line sorafenib. Frontline systemic therapy is poorly defined in certain subgroups of HCC such as Child-Pugh B and post-transplant recurrent HCC. The landscape of frontline HCC treatment is rapidly changing, and this article reviews the most recent treatment approaches to frontline therapy for advanced HCC.

Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study.

This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45-79), 60% had Rai stage 3-4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300-2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4-5 months) chemotherapy-free precision therapy for previously untreated CLL.

Frontline Treatment of the Young, Fit Patient with CLL: A Canadian Perspective.

From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The prevalence of this population ranges between 2 and 22 per 100,000 persons in Canada and varies by region. Until recently, fixed-duration fludarabine-based chemoimmunotherapy (CIT) was the primary treatment option in Canada for this patient population. The ECOG1912 trial has since demonstrated that ibrutinib and rituximab therapy are as effective as fludarabine-cyclophosphamide-rituximab (FCR) in this population. The ALLIANCE trial showed that rituximab added no incremental benefit to ibrutinib. Canadian payors and physicians adopted ibrutinib monotherapy as the CLL standard of care, even in the young, fit population, although frontline ibrutinib therapy is often reimbursed by provincial public drug plans only in patients with high-risk disease or those who are unfit to receive fludarabine. Young, fit patients with CLL and their physicians may now choose between continuous ibrutinib monotherapy and fixed-duration CIT with FCR. Factors affecting this choice include patient preference and the short- and long-term toxicity profiles of both regimens, and a risk-based algorithm is provided. As new continuous-therapy options enter the market, all treatment choices present benefits and risks that must be communicated to the patient.

Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis.

PURPOSE: The goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). METHODS: The efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative ranking area (SUCRA) values. Expert opinion from 2 hematologists was sought to validate results. FINDINGS: Both networks showed a significant improvement in PFS for acalabrutinib + obinutuzumab over all comparators. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B. Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax + obinutuzumab in Network B but not Network A. Although OS HRs all favored acalabrutinib, most were not significant and were characterized by wide CrIs, indicating a high level of uncertainty. Acalabrutinib + obinutuzumab ranked highest in terms of PFS improvement (SUCRA values, 98% and 100%) and OS improvement (SUCRA values, 92% and 94%), followed by acalabrutinib monotherapy (SUCRA values for PFS, 88% and 90%; OS, 83% and 87%) in Networks A and B, respectively. IMPLICATIONS: Acalabrutinib was associated with favorable PFS and OS compared with frontline CLL therapies and ranked highest in treatment efficacy over the other comparators. The NMA was limited by heterogeneity in patient baseline characteristics across trials, variable treatment regimens, and short study follow-up times. Despite these limitations, the NMA provides insights into the relative efficacy of acalabrutinib compared with frontline CLL therapies in the absence of head-to-head clinical trials.

Frontline Management of Epithelial Ovarian Cancer-Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research.

Epithelial ovarian cancer (EOC) is the most common histology of ovarian cancer defined as epithelial cancer derived from the ovaries, fallopian tubes, or primary peritoneum. It is the fifth most common cause of cancer-related death in women in the United States. Because of a lack of effective screening and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer consists of a combination of cytoreductive surgery and systemic chemotherapy. Despite the advances with new cytotoxic and targeted therapies, the five-year survival rate for all-stage EOC in the United States is 48.6%. Delivery of up-to-date guideline care and multidisciplinary team efforts are important drivers of overall survival. In this paper, we review our frontline management of EOC that relies on a multi-disciplinary approach drawing on clinical expertise and collaboration combined with community practice and cutting edge clinical and translational research. By optimizing partnerships through team medicine and clinical research, we combine our cancer center clinical expertise, community practice partnership, and clinical and translational research to understand the biology of this deadly disease, advance therapy and connect our patients with the optimal treatment that offers the best possible outcomes.

Current trials for frontline therapy of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin's lymphoma that generally affects older individuals. However, the use of high-dose therapy and autologous stem cell transplant has improved significantly the prognosis of this hematological malignancy, but at the cost of increased toxicities, such as acute toxic death and secondary malignancies. But thanks to a rising understanding of the biology of MCL, the explosion of specifically targeted new efficacious agents, immunotherapy agents, and cellular therapies in the frontline setting, the prognosis of MCL is expected to improve dramatically.The initial treatment of MCL is currently not standardized and the therapeutic landscape of MCL is rapidly evolving. This review provides an extensive overview of the current frontline therapy trials for MCL and presents the results of innovative regimen, including some integrating novel agents and desintensified chemotherapy.

Frontline treatment of acute myeloid leukemia in adults.

Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients' age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40-50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30 to 40% up to 80 to 90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the "7+3"regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the "7+3" regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future.