Reduced-dose Chemotherapy Research Articles

Treatment approaches and survival outcomes in elderly colorectal cancer patients: a single-center comparative study.

Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3months, P = 0.590) or PFS (9.8 vs. 7.5months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients.

Reduced-dose chemotherapy followed by blinatumomab in induction therapy for newly diagnosed B-cell acute lymphoblastic leukemia.

Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes. We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy. At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10-4 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported. Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.

Feasibility of Quality of Life Assessment in Patients with Lymphoma Aged ≥80 Years Receiving Reduced-Intensity Chemotherapy: A Single-Institute Study.

Quality of life (QOL) must be carefully monitored in older patients with lymphoma who are suitable for chemotherapy, but few reports have assessed QOL in older patients who received reduced-intensity chemotherapy. This study investigated QOL in patients with lymphoma aged ≥80 years to clarify the feasibility of such assessments following reduced-intensity chemotherapy. QOL was prospectively analyzed (using the QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD)] and the SF-36®, a comprehensive survey of patient health) among 13 patients (seven women) aged ≥80 years with lymphoma who received reduced-intensity chemotherapy at 4-week intervals at Kyushu University Beppu Hospital between June 2022 and August 2023. Patients were assessed at baseline, in the middle of the protocol, at the end of the protocol, and 6 months after the end of the protocol. The overall response rate was 69%. Almost all severe adverse events (10 patients) occurred during early cycles (cycles 1-2). Common adverse events included hematological toxicities such as neutropenia (10 patients). The daily activity (p = 0.048) and social attitude (p = 0.027) scores of the QOL-ACD and the general health perception (p = 0.044) and social functioning (p = 0.030) scores of the SF-36® were significantly improved during and after chemotherapy. Reduced-dose chemotherapy, if implemented before treatment selection, might permit evaluations of QOL in older patients aged ≥80 years; further investigation is warranted.

Reduced-Dose Chemotherapy Followed By Blinatumomab As Induction Therapy in Treatment of Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia - Interim Results from a Multicenter, Single-Arm, Phase 2 Study

Introduction: Although intensive pediatric chemotherapeutic regimens have shown good efficacy in the treatment of Philadelphia Chromosome-negative (Ph-negative) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in adults, the high incidence of chemotherapy-related toxicities limits their use. Blinatumomab, a CD3/CD19 bispecific T-cell antibody, has shown high efficacy in relapsed/refractory or minimal residual disease (MRD) positive BCP-ALL; however, the efficacy of single-agent blinatumomab does not meet the treatment needs of adult patients. Therefore, combining low-intensity chemotherapy with blinatumomab could be a better induction regimen for newly diagnosed adult patients with BCP-ALL. Methods: This multicenter, single-arm, phase 2 trial (NCT05557110) enrolled adult patients (aged 15-59 years) with newly diagnosed Ph-negative BCP-ALL. The induction regimen comprised reduced intensity chemotherapy (idarubicin 8 mg/m 2 on day 1, vindesine 4 mg on day 1, and dexamethasone 9 mg/m 2/day from day 1-7) followed by 2 weeks of blinatumomab (9 ug/day from day 8-14, 28 ug/day from day 15-21). The primary endpoint was to assess the overall response rate (ORR=complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi]) of this induction regimen. Secondary endpoints were MRD negativity (&amp;lt;1x10 -4 by flow cytometry), event-free survival (EFS), overall survival (OS) and safety. Bone marrow evaluation and one intrathecal injection chemotherapy were performed on day 22±2. Patients not achieving ORR continued blinatumomab for another 2 weeks (28 ug/day from day 1-14), followed by bone marrow re-evaluation. Consolidation therapy was given after achieving ORR with recommended multidrug combination chemotherapy (including high-dose methotrexate or cytarabine combined with asparaginase) or alternating with blinatumomab (28 ug/day for 28 days). If allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not performed, consolidation therapy needs at least 4 courses before 2 years of maintenance therapy. Results: Interim results are presented here.By July 6, 2023 (data cut-off), 25 patients were enrolled with a median age of 42 years (range: 15-53); 68% were females. The Eastern Cooperative Oncology Group Performance Status score ranged from 0-1. Eight (32.0%) patients had poor cytogenetic risk factors, including 3 with P2RY8::CRLF2, 2 with hypodiploidy, 2 with KMT2A rearranged and 1 with alterations of IKZF1 (Table 1). The bone marrow evaluation done in 19 patients on day 8 prior to blinatumomab treatment showed that none of the patients had got ORR. All 21 (100%) patients evaluable for the primary endpoint attained CR/Cri - 19 at the end of 2 weeks of blinatumomab and the remaining 2 after another 2 weeks of blinatumomab (Table 2). The MRD negativity rate was 90.5% (19/21) after 2 weeks of blinatumomab which increased to 95.5% (20/21) after another 2 weeks of treatment with blinatumomab. In 21 patients evaluated for safety, blinatumomab-related cytokine release syndrome was reported in 10 (47.6%) patients (grade 1: n=6, grade 2: n=3 and grade 3: n=1). No incidence of neurotoxicity was reported. Febrile neutropenia was reported in 4 (19%) patients (all ≥grade 3). The non-hematological AEs reported were fever in 7 (33.3%) patients (any grade), increased ALT in 10 (47.6%) patients (any grade) and infections in 4 (19%) patients, including pneumonia in 2 and sepsis in 2 (all ≥grade 3). The median duration of neutrophil deficiency (&amp;lt;0.5×10 9/L) and platelet deficiency (&amp;lt;20×10 9/L) during induction therapy was 9 days (range: 0-20) and 1 day (range: 0-18), respectively. The median follow-up time was 4 months and no relapse or leukemia-related deaths were observed. The median EFS and OS were not yet reached. All enrolled patients are alive except one who died of infection after multidrug combination consolidation chemotherapy. The median cycles for consolidation were 2 (range: 1-5) with 3 patients undergoing allo-HSCT. Conclusion: Thesepreliminary results indicate that the reduced intensity chemotherapy followed by blinatumomab is an effective regimen in adults with newly diagnosed Ph-negative BCP-ALL, resulting in favorable response rates, deep remission, and low-grade treatment-related AEs. These promising findings may provide a rationale for integrating blinatumomab into future induction therapy recommendations.

SIOG2023-1-OA-101 - Randomized phase III clinical trial:Non-inferiority of reduced dose chemotherapy based on CARG

SIOG2023-1-OA-101 - Randomized phase III clinical trial:Non-inferiority of reduced dose chemotherapy based on CARG

Efficacy and safety of reduced-dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real-world observational study.

Recently, chemotherapy plus immunotherapy has achieved remarkable efficacy in lung squamous cell carcinoma (LUSC). However, some patients, especially frail people, cannot tolerate full-dose chemotherapy in the real world. To reduce toxicity, appropriate dose reduction in chemotherapy is necessary. Therefore, this study aimed to demonstrate the efficacy and safety of reduced-dose chemotherapy plus immunotherapy in LUSC patients in the real world. A real-world observational study was conducted concerning patients who received chemotherapy plus immunotherapy in our situation. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. Between December 2018 and January 2022, 110 patients were enrolled, of whom 54 patients were chemotherapy reduced-dose group and 56 patients were chemotherapy standard-dose group. The ORR in the reduced-dose group is similar to standard-dose group (85.19% vs. 71.43%, p = 0.082). Similar DCR were observed (100% vs. 94.64%, p = 0.086). Median PFS was 12 months in the reduced-dose group and standard-dose group, respectively. Median OS was 15 months and 16 months in the reduced-dose group and standard-dose group, respectively. We reported a lower incidence of grade 3-4 toxicity in the reduced-dose group compared with standard-dose group (27.78% vs. 42.86%, p = 0.100). The major toxic reactions were better alleviated in the reduced-dose group than in the standard-dose group, especially in the thrombocytopenia (p = 0.044), peripheral nerve damage (p = 0.001), gastrointestinal reactions (p < 0.0001), and fatigue (p = 0.001). The modified regimen with attenuated doses of chemotherapy in combination with immunotherapy was effective and well tolerated in patients with LUSC. The efficacy of this modified regimen is similar to that of the full-dose regimen.

Treatment of lymphoid malignancies in patients with primary immunodeficiencies associated with DNA repair defects

Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia (AT; Louis–Bar syndrome) are primary immunodeficiencies (PID) associated with chromosome instability and DNA repair defects that predispose individuals to an increased risk of various malignancies. In our study, we retrospectively analyzed clinical characteristics and outcomes of 28 cancer cases in 14 patients with AT and 10 patients with NBS who had been treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between January 2007 and December 2022. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The most common type of malignancy was mature B-cell non-Hodgkin lymphoma (B-NHL) (42%), with diffuse large B-cell lymphoma (DLBCL) accounting for 91% of all B-NHL cases. Other cases included T-cell acute lymphoblastic leukemia (ALL) (n = 3), B-cell ALL (n = 2), Hodgkin lymphoma (n = 3), NK/T-cell lymphoma (n = 1), T-cell lymphoblastic lymphoma (n = 1), peripheral T- cell lymphoma (n = 2), medulloblastoma (n = 1) epithelioid rhabdomyosarcoma (n = 1), T-cell prolymphocytic leukemia (n = 2). A total of 4 patients were diagnosed with second malignancies (2 children with AT and 2 children with NBS. The diagnosis of PID was suspected or confirmed before the initiation of cancer therapy in 62% of AT patients and in 100% of NBS patients. Treatment was given in accordance with standard protocols with chemotherapy dose modifications. A total of 93% of patients with AT and 80% of patients with NBS required dose reduction. The level of response was quite high: 81% of patients with AT and 58% of patients with NBS achieved complete remission. According to our data, the use of reduced-dose chemotherapy regimens helps to achieve an acceptable toxicity profile without reducing the overall effectiveness of treatment.

Tyrosine kinase inhibitors and reduced-dose chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

ABSTRACT Objectives: To compare the outcomes of tyrosine kinase inhibitors (TKIs) in combination with reduced-dose chemotherapy with those of standard induction chemotherapy, as well as the outcomes between chemotherapy and transplantation, in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Methods: We retrospectively reviewed cases of Ph+ ALL treated with TKIs and combination chemotherapy. The patients were allocated to either the TKIs with reduced-dose chemotherapy group or the TKIs with standard chemotherapy group. In additions, patients were further stratified into either the transplant group or the non-transplant group. Results: The complete remission rate (88.7% vs. 83.9%, p = 0.372), major molecular response (58.9% vs. 56.0%, p = 0.750), molecular complete response (20.5% vs. 22.0%, p = 0.891), and early mortality rate (3.2% vs. 3.5%, p = 0.922) were similar between the TKIs with reduced-dose chemotherapy group and the TKIs with standard chemotherapy group. The proportions of lung infections, bloodstream infections, patients with >21 days of hospitalization, the total costs, transfusion costs, and antimicrobial costs were higher in the standard chemotherapy group than in the TKIs with reduced-dose chemotherapy group. The 3-year overall survival rates (59.0% [95% CI, 46.6–74.7%] vs. 38.4% [95% CI, 29.9–49.4%]) and disease-free survival rates (48.6% [95% CI, 34.2–69.1%] vs. 32.0% [95% CI, 23.5–43.7%]) were significantly better in the transplant group than in the non-transplant group. Conclusion: An induction regimen combining TKIs with reduced-dose chemotherapy and transplantation during the first complete remission remains a suitable and effective option for patients with Ph+ ALL.

Abstract 521: CD45 targeted engineered toxin bodies deplete hematopoietic and malignant cells

Abstract CD45 is highly expressed on the cell surface of all nucleated hematopoietic cells, including malignant cells of B, T and myeloid lineage. CD45, a receptor tyrosine phosphatase that has important roles in antigen receptor signaling, has multiple isoforms that are differentially expressed on immune cell subsets. Targeting of CD45 with antibody-based therapies, tested in conjunction with reduced dose chemotherapy and radiation regimens, has shown promise in preclinical models and clinical trials as a conditioning therapy for bone marrow transplant (BMT), although these approaches are associated with safety limitations. A single agent, targeted conditioning method could increase patient safety and eliminate genotoxic effects associated with the conditioning regimens. Conditioning therapy by depletion of CD45 positive cells specifically has potential applications in oncology as well as non-oncologic, hematopoietic disease settings where engraftment of donor or modified stem cells could provide benefit. Engineered toxin bodies (ETBs) are comprised of a proprietarily engineered form of Shiga-like Toxin A subunit (SLT-A) genetically fused to antibody-like binding domains. ETBs work through novel mechanisms of action and are capable of forcing internalization, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation of ribosomes. Targeted ETBs are being developed to specifically target and destroy CD45 expressing cells. ETBs targeting CD45 specifically bind to, internalize into and then trigger cell death of the target cells in vitro. ETBs have been designed using antibody fragments that recognize all isoforms of CD45. The CD45 targeted ETB has shown high potency in immortalized blood cancer cell lines of T cell, B-cell and eosinophil origin, including leukemia and lymphoma cell lines. Additionally, the ability of the CD45 targeted ETBs to deplete primary cells from healthy donors has been demonstrated. The direct cell kill activity of the CD45 targeted ETBs have the potential to deplete immune cells in the periphery and the bone marrow, as well as to deplete malignant hematological cells expressing CD45. In vivo depletion of human immune cells in murine models by CD45 targeted ETBs will be evaluated. Citation Format: Aimee Iberg, Garrett L. Robinson, Sara LeMar, Joseph D. Dekker, Jay Zhao, Hilario J. Ramos, Melissa M. Singh, Erin K. Willert. CD45 targeted engineered toxin bodies deplete hematopoietic and malignant cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 521.

Treatment of Elderly Patients with Acute Promyelocytic Leukemia: A Real Life Experience of the “Rete Ematologica Lombarda”

Background Acute promyelocytic leukemia (APL) in the elderly has a favourable outcome in a significant proportion of patients (pts). Elderly and frail pts are usually treated with attenuated treatment schedules, mostly "according to medical judgment". The combination of all-trans retinoic (ATRA) and anthracycline-based chemotherapy (CT) has been the mainstay of treatment for many years. Alternative approaches, such as arsenic trioxide (ATO) and gentuzumab ozogamicin (GO) have recently been tested with success in this setting, even though no large series of elderly pts treated with CT-free first-line treatment have been published yet. Moreover, neither a "standard of care approach" nor a specific prognostic score system have been developed to guide physician in choosing the most adequate treatment schedule in this setting. Objective Aim of the present preliminary survey was to assess genetic and clinical features of APL in pts over 60 yrs. This cut off reflects the definition of "elderly patient" in most Italian APL GIMEMA trials. Moreover, both the real life outcome and safety data after either conventional anthracycline-based CT or alternative CT-free approaches were analysed. OS, response rate to either regimens and adverse event occurrence were collected. Methods This retrospective multicenter REL (Rete Ematologica Lombarda) survey, enrolled a total of 101 consecutive APL pts aged ≥60, treated between 2000-2018. Demographics, clinical data and therapy outcome data were recorded in a dedicated patient's report form. Statistical analysis was performed using the Kaplan Maier method, Log-rank test and Cox regression. Results For analysis, pts were grouped into different categories according to age and fitness. Tables 1 and 2 summarise clinical charcteristics and treatment administered. Performance status (PS) and number of comorbidities increase with age. Twentynine of 102 (28,4%) and 9/102 (8,8%) pts had a history of or subsequently developed a solid tumor respectively. High frequency of additive cytogenetic abnormalities was observed as well. CT+ATRA was preferentially administered, mostly with attenuated intensity, to younger pts with better PS, while ATO+ATRA was preferred in pts with reduced cardiac function and ATRA monotherapy was reserved to frail or over 80 yrs old pts. Rates of differentiation syndrome or infections or cardiac events were similar in the different treatment groups. Overall, complete remission (CR) rate after induction therapy was 94.16% [CI95%: 87,5%-97,8% ]. At a median follow-up of 40 mos (range 0-199), the overall relapse rate was 24%. Median time to relapse was 7 mos in 1/8 (12,5%) ATRA monotherapy treated pts and 13 mos (range 5-66) in the 23/68 (33,8%) pts receiving CT+ATRA. No relapse occurred among the 22 pts treated with ATO+ATRA (p 0.005). OS and EFS were significantly associated with pts' age (HR 9% and 7.6%; p&lt;0.001); 35/101 (34,6%) deaths were observed, due to early deaths/toxicity (9/35; 25,7%), relapse or progressive disease (9/35; 25,7%), concurrent neoplasia (10/35; 28,5%), other cause (6/35; 17,1%). Deaths in ATO+ ATRA group occurred after CR, because of neoplasia. Both EFS (median 34 months , range 0.03-199) and OS were significantly higher in the ATO-based therapy group (p&lt;0.0001). (Fig. 1-2) Conclusion This survey confirms that elderly and frail APL pts may benefit from ATO-based regimens. Reduced-dose antracycline-based CT, appears to be less effective, with high rate of relapse in elderly pts. Scoring systems and prospective data are needed in order to better define treatment strategies aiming to further improve outcome in this challenging but growing population. Disclosures Rossi: Daiichi-Sankyo: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria.

Clinical feature of very elderly malignant lymphoma patients unfit for chemotherapy

Abstract Introduction Malignant lymphoma is a curable disease by chemotherapy, and therefore very elderly patients with good condition can undergo reduced-dose chemotherapy and achieve longer survival. But there are few studies about those who are frail and cannot undergo chemotherapy. We studied about the outcome of palliative treatment for such patients. Methods From April 2011 to December 2018, 529 malignant lymphoma patients have visited our department. Eighty-five patients were aged more than 80. Among them, 61 patients underwent reduced standard chemotherapy, course observation was selected in 8 for indolent lymphoma, and palliative treatment in 9 and best supportive care (BSC) in 7 patients. In this study, we focused on 16 patients (9 palliative treatments and 7 BSCs). Results Histological type contained 9 diffuse large B-cell lymphomas (DLBCLs), 2 T-cell lymphomas and 5 other types. Clinical stage was divided into 6 limited and 8 advanced stages and 2 no data. The reasons of unfitness for chemotherapy were 7 performance status>2, 5 dementia, 4 combinations with other malignancy and 3 latent tuberculosis infections. Treatments were performed as 2 radiotherapies (RT), 6 oral steroids (contained 2 rituximab) and 1 surgical resection. Mean survival time was 452 days, but the distribution was clearly divided into very short group ( 1000 days). Causes of death were 10 lymphomas, 1 lung cancer 1 abdominal aneurysm rapture and 1 senility. Final treatment institutes were 2 university hospitals, 7 local hospitals, 5 clinics and 2 palliative care hospitals. A DLBCL case who achieved complete remission with RT and oral etoposide is presented. Conclusion The most patients without standard chemotherapy lived only for 3 months but one quarter lived for 3 years. Palliative therapies as possible might have some advantages in malignant lymphoma patients unfit for chemotherapy.

Present status and research progresses in treatment of acute myeloid leukemia patients aged over 80 years

The number of acute myeloid leukemia (AML) patients aged over 80 years are increasing year by year. They have poor treatment effects and shorter survival period because of elderly age, more underlying diseases, poor tolerance to chemotherapy. At present, there are many treatments reported, including supportive therapy, standard-dose chemotherapy, reduced-dose chemotherapy, demethylation therapy, hematopoietic stem cell transplantation(HSCT) and adoptive cellular immunotherapy, and various treatments have achieved some good effects in AML patients aged over 80 years. However, the survival of this group of patients is still poor. And there are lack of unified and effective therapeutic strategies for elderly patients with AML. This article reviewed the present status and research progresses on treatment of AML aged over 80 years. Key words: Leukemia, myeloid, acute; Aged; Life support care; Prognosis; Drug therapy

10-Day Low Dose Decitabine Regimen for Elderly Acute Myeloid Leukemia Patient Maintenance Treatment

BackgroundAcute myeloid leukemia (AML) is a malignant hematologic disease with high incidence in the elderly peoples. The median age of onset is 65 years. There is no standard chemotherapy regimen for elderly AML, especially for AML patients older than 70 years old. Six to eight courses of low-dose or reduced-dose chemotherapy were commonly used in clinical treatment. However, most patients. However, most patients relapsed within six months after chemotherapy. How to prolong the survival of elderly patients with AML is a realistic problem that needs to be urgently solved.Patients and MethodsFrom Jan 2017 to May 2018, six elderly patients with AML in our center include in the study. The median age was 74 (70-78) years. According to cytogenetics and molecular mutation, 1 patient were favorable risk with t (8, 21) and AML1-ETO, 3 patients were intermediate risk with karyotype abnormality, and 2 patients were unfavorable risk with complex karyotype and FLT3-ITD mutation. One patient received complete remission (CR) after IA induce scheme, and then, he received 4 courses of DA regimen for consolidation therapy. At last, he stopped chemotherapy because of severe atrial fibrillation and heart failure. Other 5 patients treated with 4-8 courses of decitabine (Dec) +CAG or HAG regimen. Minimal residual disease (MRD) of four patients were negative and two patients were positive before include in the study. Six patiens were given 10-day low dose Dec regimen treatment (5mg/m2/day×10 days) for every six weeks, until AML progress.ResultsFor 2 MRD positive patients, after 10-day low dose Dec regimen treatment, one patient MRD turn to negative, one patient MRD remained positive, and died after 4 months. Till Jul 2018 (median observation time 10 months), 5/6 patients remained CR and survival with better quality of life. the most common treatment-emergent adverse events (TEAEs) were related to hematocytopenia. The most significant reduction of blood cells was hypoleucocytosis, and mainly in the first 2 courses of G-Dec treatment.ConclusionPreliminary research shows 10-day low dose Dec regimen treatment has Significant effect and mild side effect on the survival of elderly AML patients. The multicenter, randomized controlled clinical study will conduct to further verify its effectiveness and safety. DisclosuresNo relevant conflicts of interest to declare.

Abstract P5-18-02: Nab-Paclitaxel-based therapy in the first line treatment of metastatic breast cancer (IBCSG 42-12/BIG 2-12 SNAP): Impact of different schedules on quality of life

Abstract Background: The randomized phase II SNAP trial assessed three alternative reduced maintenance chemotherapy regimens using nab-Paclitaxel after a short term induction phase at conventional doses as first line treatment in patients (pts) with metastatic breast cancer (MBC). For all three regimens median progression-free survival was greater than achieved with full dose docetaxel (historical reference). Symptom palliation and quality of life (QoL) are important when deciding on therapeutic agents and schedules in MBC pts. Methods: Of the 258 pts with MBC enrolled from April 2013 to August 2015 in the SNAP trial, 255 were included in the QoL analysis. Pts were randomized to three arms, each receiving the same induction chemotherapy based on 3 cycles of nab-Paclitaxel 150 mg/m2 dd 1, 8, 15 Q28, which was reduced to 125 mg/m2 after a safety review. The schedules of nab-Paclitaxel in maintenance therapy differed in each arm: Arm A) 150 mg/m2 dd 1,15 Q28; Arm B) 100 mg/m2 dd 1,8,15 Q28; Arm C) 75 mg/m2 dd 1,8,15,22 Q28. Pts completed a QoL form to assess global and symptom-specific indicators (range 0-100) at baseline, and at day 1 of every cycle for the first 12 cycles on treatment, or until treatment discontinuation. Changes in QoL scores during induction (day 1 cycle 4 − baseline) and maintenance (day 1 cycle 12 – day 1 cycle 4) therapy were summarized descriptively per arm. Treatment effects on changes in QoL during maintenance therapy were analyzed by repeated measurement models including timepoints (from day 1 of cycle 4 to day 1 of cycle 12), induction start dose, age, and treatment arms as covariates. Results: During induction therapy, mean changes [SD] in hair loss (Arm A:−70.2 [41.9]; Arm B: −77.3 [34.5]; Arm C: −72.6 [32.8]), sensory neuropathy (Arm A: −19.0 [25.2]; Arm B: −20.6 [22.7]; Arm C: −18.8 [23.8]), and treatment burden (Arm A: −12.9 [33.4]; Arm B: −13.4 [33.5]; Arm C: −11.4 [34.8]) showed the most pronounced worsening. During maintenance therapy, scores for sensory neuropathy remained impaired without worsening. No significant differences in changes for sensory neuropathy or the other symptoms were seen between arms, except for hair loss, with pts in arm C (mean difference 10.91; 95% CI [0.35, 21.48]; p=0.04) ] and B (mean difference 18.55; 95% CI [7.52, 29.59]; p=0.001) reporting a greater improvement compared to those in arm A. Pts in arm C reported a significantly greater improvement in mood compared to arm A (mean difference 13.34; 95% CI [6.08, 20.60]; p&amp;lt;0.001) and arm B (mean difference 9.62; 95% CI [2.84, 16.40]; p=0.01)]. Conclusion: The effectiveness of alternative maintenance chemotherapy schedules with reduced doses after a short term induction phase at conventional doses must be weighed against a substantial worsening in sensory neuropathy during induction therapy, and scores continuing to be impaired without worsening with prolonged administration. During maintenance therapy, improvements were seen in the perception of hair loss and in mood, particularly in Arm B and C, with a similar tendency seen for some other QoL domains. A more frequent administration of reduced dose chemotherapy agents is favorable with respect to QoL in this setting. Citation Format: Ribi K, Sun Z, Jerusalem G, Hasler-Strub U, Colleoni M, von Moos R, Cortés J, Vidal M, Hennessy B, Walshe J, Amillano Parraga K, Morales Muriilo S, Pagani O, Barbeaux A, Bortsnar S, Maibach R, Regan MM, Gennari A, Bernhard J. Nab-Paclitaxel-based therapy in the first line treatment of metastatic breast cancer (IBCSG 42-12/BIG 2-12 SNAP): Impact of different schedules on quality of life [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-02.

Antineoplastic chemotherapy in Jehovah's Witness patients with acute myelogenous leukemia refusing blood products – a matched pair analysis

ABSTRACTBackground: Acute myelogenous leukemia (AML) may be cured in a substantial number of patients using intensive chemotherapeutic regimens leading to temporary severe myelosuppression. Patients belonging to the denomination of Jehovah's Witnesses (JW), however, are bound by their religious convictions not to accept blood products and are therefore at higher risk for life-threatening events. Reports how to handle this challenge are mainly anecdotal.Material and methods: We here report in much more detail about our experience with nine patients belonging to the denomination of JW who were treated for AML in our department from 1998 to 2007 and who explicitly wished to receive chemotherapy without blood transfusions.Results: Reduced dose induction chemotherapy administered by several treatment cycles to prevent sustained myelosuppression still led to complete remissions in three out of nine of JW patients but was associated with a high rate of relapse. No durable remission was achieved. The overall hazard ratio for death was 12.1 compared to a matched control group treated with full transfusion support. The predominant cause of non-AML mortality was severe anemia (four out of five early deaths) and uncontrollable bleeding (n = 1).Conclusion: Reduced dose chemotherapy without transfusion support in JW suffering from AML is associated with a lower rate of remission, high mortality by severe anemia and very low chances for long-term remissions. Less hematotoxic treatment options including hypomethylating agents or molecular targeted therapies with intensive consolidation after improvement of bone marrow function are promising for these patients but need further investigation.

Impact of comorbidities on outcomes of elderly patients with diffuse large B-cell lymphoma.

International prognostic index (IPI) has remained the primary prognostic tool in diffuse large B cell lymphoma (DLBCL) for more than 20 years. Even though the disease is more common in older population, the impact of comorbidities, dose reductions, and treatment-related adverse events (TAEs) on the outcome in elderly DLBCL patients has not been well established. We studied 413 consecutive patients aged ≥ 60 years who were treated at the Cleveland Clinic. The median age at diagnosis was 69 years, 58% of patients had high IPI score, and 85% had low Charlson comorbidity index (CCI). Forty percent of patients required dose reductions during treatment, 78% achieved CR, and 70% experienced at least one grade II-IV TAE. High IPI score, high CCI, reduced dose chemotherapy, TAE, and hospitalization were significant predictors of death and relapse. In multivariable analysis, high IPI and CCI were independent predictors of overall and progression free survival. A simple model combining IPI and CCI could reliably distinguish three prognostically separate risk groups. Our results suggest that incorporation of CCI in current prognostic models can improve prognostication of older DLBCL patients and CCI might be a valuable tool in evaluating the eligibility of older patients for clinical trial enrollment.

P3.02c-093 A Prospective, Randomized, Multicenter, Phase III Study, Comparing rhTPO with rhIL-11 Treating CIT (NCT02344979): Topic: IT Clinical

Chemotherapy-induced thrombocytopenia (CIT) is a common dose limiting toxicity of clinical chemotherapy drugs, which may lead to reduced dose chemotherapy or delay chemotherapy time, and even terminate chemotherapy treatment. This is the first randomized, open-label, multicenter, phase III study to compare the efficacy and safety of prophylactic treatment for thrombocytopenia in China. We tried to investigate the efficacy and safety of preventive application with rhTPO or rhIL-11 to protect against CIT in advanced non-small-cell lung cancer (NSCLC) patients. From June 2009 to July 2016, 108 patients with NSCLC who were receiving the first-line platinum-based chemotherapy suffered from severe thrombocytopenia(the nadir of platelet counts＜50×109/L) during the prior chemotherapy cycle. They were randomized to rhTPO arm or rhIL-11 arm in the following chemotherapy cycle, and the chemotherapy regimens and drug doses were consistent with that in the prior and following cycle (GC Gemcitabine 1000-1250 mg/m2, D1 and D8; Carboplatin dosing by AUC value=5, D1; Q3W) or GP (Gemcitabine 1000-1250 mg/m2, D1 and D8; Cisplatin 75 mg/m2, D1; Q3W). 77 patients (56males, 21 females) were enrolled in rhTPO arm and 31 patients (18 males, 13 females) were enrolled in rhIL-11 arm. There were no statistical difference between two arms in terms of gender, age and the nadir of platelet counts during prior chemotherapy cycle(P＞0.05). rhTPO (15000U/d) was injected subcutaneously on the 2nd, 4th, 6th, 9th Day after the initiation of chemotherapy, and IL-11(3mg/d) was injected subcutaneously per day from Day 9 to Day15 after the initiation of chemotherapy. Blood routines were conducted to test before chemotherapy initiation and the 3rd, 5th, 7th, 9th, 11th, 13th, 15th, 17th, and 21st day after chemotherapy. Toxicity and efficacy were monitored. In the following chemotherapy cycle there were no statistical difference between rhTPO arm and rhIL-11 arm on the following indexes: the nadir of platelet counts (62.6±39.4×109/L vs. 52.8±36.8×109/L, P＞0.05), the maximum platelet counts (223.5±127.3×109/L vs. 245.8±158.7×109/L, P＞0.05), duration of platelet counts less than 50×109/L[Median (95%CI): 4.0 (3.0-5.0) days vs. 4.5 (3.0-9.0) days, P＞0.05], time of platelet count recovered to 75×109/L [Median (95% CI): 5(3-7) days vs. 6 (4-8) days, P＞0.05] and to 100×109/L[median (95% CI): 6(6-8) days vs. 6 (5-9) days, P＞0.05]. Drug-related adverse events in rhTPO arm were less than those of rhIL-11 arm (5 cases (6.49%) in rhTPO arm, 8 cases (25.8%) in rhIL-11 arm, P<0.05). Although there is no statistical difference on efficacies, prophylactic administration of rhTPO is safer and more convenient than that of rhIL-11 in advanced NSCLC patients.

Outcomes of very elderly patients with aggressive B-cell non-Hodgkin lymphoma treated with reduced-dose chemotherapy.

Although the number of patients aged 80years or older with aggressive B-cell non-Hodgkin lymphoma (B-NHL) has increased in the clinical setting, management has been challenging due to lower tolerability. The aim of the present study was to evaluate the efficacy and safety of reduced-dose chemotherapy for very elderly patients. We retrospectively analyzed the clinical outcomes of patients aged ≥80years old with diffuse large B-cell lymphoma (n=58) or grade 3 follicular lymphoma (n=3). Patient ages ranged from 80 to 93years old, with a median of 83years old. Twenty-four patients were treated with CHOP or THP-COP, the dosages of which were variably reduced, in combination with rituximab (R-vCHOP), while another 24 patients were treated with R-miniCHOP. Twelve R-vCHOP and 16 R-miniCHOP patients completed the chemotherapy cycles. The estimated 2-year progression-free and overall survival rates in the R-vCHOP and R-miniCHOP groups were 53 and 39% (P=0.92) and 53 and 48% (P=0.95), respectively. Performance status ≥2, lactate dehydrogenase level >normal, serum albumin ≤3.5g/dL, C-reactive protein ≥2.0mg/dL, age-adjusted International Prognostic Score 2/3, and withdrawal from the chemotherapy cycle were associated with poor survival. The frequency of chemotherapy-related hospitalization during the second or later cycles was significantly less in the R-miniCHOP group. The efficacies of R-vCHOP and R-miniCHOP were similar in patients aged ≥80years old with aggressive B-NHL. The reduced frequency of hospitalization observed for R-miniCHOP treatment is beneficial for very elderly patients.

Prognostic Value of Neuro-Psychological and Biological Factors in Clinically Fit Older Patients with Hematological Malignancies

BACKGROUND: A Comprehensive Geriatric Assessment (CGA) is recommended to detect vulnerable cancer patients for whom chemotherapy may lead to severe impairment on functionality, quality of life, or survival. Although CGA is useful for a better management of older patients with unsuspected problems, little is known about the reliability of CGA - or G8 screening tool - to optimize the therapeutic approach in a specific patient with a malignant hemopathy. Particularly, the prognostic value of cognitive functions, psychological status and other selected biological factors in older patients with hematological malignancies admitted to receive chemotherapy, are poorly investigated.AIM: To assess in clinically fit (go and slow go) patients with malignant hemopathies, the reliability of G8 screening and CGA as a prognostic tool to predict overall survival (OS) and particularly, the predictive value of neuro-psychological and biological factors, in terms of one-year OS.POPULATION AND METHODS: Between Oct 2010 and June 2013, G8 and CGA were proposed to 107 consecutive older patients (65+-yrs) with hematological malignancies, admitted to the hospital and judged clinically fit, by their refereeing physicians, to receive chemotherapy. An initial full-dose or reduced-dose chemotherapy has been administrated to these patients according to a multidisciplinary team decision. The nutritional status was screened by MNA and the cognitive functions by MMS and MoCARESULTS: Ninety patients -completely assessed for G8 and CGA- were evaluable for one year OS; Non Hodgkin’s Lymphoma (53%), Multiple myeloma (16%), Acute Myeloid Leukemia and Myelodysplastic Syndrome (15%), Chronic Lymphocytic Leukemia (14%) and Myeloproliferative Neoplasms (2%). Median age is 74 (65-89) yrs. 56% are males. 72% and 80%, were considered as “vulnerable” when evaluated with G8 (≤14.5) or CGA (≥2 impairments), respectively. The area under ROC-curve of G8 compared to CGA was 0.749 ± 0.051 (sensibility = 79.2% and specificity =55.6%). During the first year of follow-up, 28% (n=22) of older patients treated for hematological malignancies died. The leading cause of death (82%) was indeed the disease progression. Retrospectively, neither the G8 nor the CGA total score had an impact with the initial treatment choice and were not predictive for one-year OS. In addition, regarding patients characteristics, in a multivariate analysis (Cox proportional hazard model), age (p=0.015; HR=1.12) and diagnosis (p<0.001; HR=7.2), were major prognostic factors in terms of OS. Regarding specific CGA items, a multivariate analysis concluded that unsuspected cognitive impairment (evaluated with a MMS and a MoCA) had the strongest prognostic value (p=0.03; HR=3.560) in terms of OS.DISCUSSION: In our clinically fit hematological patients, a poor G8 or CGA score does not translate into a worse survival, more likely because of two reasons: the disease itself remains the major cause of death and malnutrition, a reversible impairment after effective treatments, strongly impacts on G8 and CGA. The objective of an effective screening tool should thus be the identification of the population who could benefit from optimal treatment combined with an comprehensive management of unsuspected specific problems.CONCLUSIONS: Our observations in “clinically fit” older hematological patients suggest that 1) the major cause of death is the disease itself and the priority should be to identify all patients susceptible to benefit from full dose chemotherapy 2) a poor G8 screening or an abnormal CGA are not specific enough and does not translate into a worse one year OS 3) some specific factors in the CGA (such as neuro-cognitive impairments) are highly correlated with one-year OS 4) age remain a continuous variable with a poor prognostic factor. Prospective trials are needed to further determine whether the combination of optimal treatment and improved management of impaired functions, including cognition, could lead to a better OS. DisclosuresNo relevant conflicts of interest to declare.

The Effect of Decreased-dose Idarubicin for Elderly Patients with Acute Myeloid Leukemia

We evaluated whether reduced-dose chemotherapy with 2 days of idarubicin (12 mg/m(2)) and 5 days of cytarabine (100 mg/m(2)) (2 + 5) is effective for patients aged 65-74 by retrospectively comparing the results with those aged 55-64 treated with 3 + 7. In 1999-2009, we treated 20 patients aged 65-74 with 2 + 5, and 23 patients aged 55-64 with 3 + 7. The complete remission rates by the first induction were 50.0 and 69.6% for older and younger groups (P = 0.203). Two-year overall survival rates were 55.9 and 32.3% for older and younger groups; 2-year rates of relapse-free survival for all these patients were 15.7 and 36.5%. The differences in overall and relapse-free survival were statistically insignificant (P = 0.726 and 0.413, respectively). The treatment results of 2 + 5 for the older group were not significantly worse compared with those of 3 + 7 for the younger. Therefore, elderly patients who do not tolerate 3 + 7 should still benefit from 2 + 5.