Multiple myeloma (MM) is the main indication for autologous stem cell transplantation (ASCT). Novel supportive therapies (e.g., granulocyte colony-stimulating factor) have significantly improved post-ASCT-related mortality; however, data on biosimilar pegfilgrastim-bmez (BIO/PEG) in this setting is lacking. This prospective cohort study compared Italian patients with MM who received BIO/PEG post-ASCT with data collected retrospectively from historical control groups from the same center who received either filgrastim-sndz (BIO/G-CSF) or pegfilgrastim (PEG; originator). The primary endpoint was time to neutrophil engraftment (three consecutive days with an absolute neutrophil count ≥ 0.5 × 109/L). Secondary endpoints included incidence and duration of febrile neutropenia (FN). Of the 231 patients included, 73 were treated with PEG, 102 with BIO/G-CSF, and 56 with BIO/PEG. Median age was 60 years and 57.1% were male. Neutrophil engraftment was reached after a median of 10 days in the BIO/PEG and PEG groups and 11 days in the BIO/G-CSF group. Among patients who achieved neutrophil engraftment earlier than this (i.e., day 9), 58% (29/50) were on PEG; of those who achieved it later (i.e., day 11), 80.8% (59/73) were on BIO/G-CSF. FN incidence was higher with BIO/G-CSF (61.4%) versus PEG (52.1%) or BIO/PEG (37.5%) (p = 0.02 among groups). Patients on BIO/PEG had less frequent grade 2–3 diarrhea (5.5%) compared with BIO/G-CSF (22.5%) or PEG (21.9%); grade 2–3 mucositis was most frequent in the BIO/G-CSF group. In conclusion, pegfilgrastim and its biosimilar displayed an advantageous efficacy and safety profile compared with biosimilar filgrastim in patients with MM post-ASCT.

CAR-T programs will burden increasingly on healthcare systems, since the implementation of these therapies involves: multidisciplinary team collaboration, post-infusion hospitalization with risk of life-threatening toxicities, frequent in hospital visits and prolonged follow-up which heavily influence patients’ quality of life. In this review we propose an innovative, telehealth-based, model for monitoring CAR-T patients: this method was used for managing a case of COVID-19 infection occurred two weeks after CAR-T cell infusion. Several benefits for management of all these aspects of CAR-T programs could be made using telemedicine: for example, telemedicine real-time clinical monitoring could reduce the COVID-19 contagion risks for CAR-T patients. Our experience confirmed feasibility and utility of this approach in a real-life case. We believe that use of telemedicine for CAR-T patients could improve: the logistics of toxicity monitoring (frequent vital sign checks and neurologic assessments), the multidisciplinary team communication (patient selection, specialists consulting, coordination with pharmacists, etc.), the decrease in hospitalization time and the reduction of ambulatory visits. This approach will be fundamental for future CAR-T cell program development, enhancing patients’ quality of life and cost-effectiveness for healthcare systems.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD ( n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant ( p = 0.599 and 0.587). Cumulative incidence of grade II–IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% ( p = 0.126) and 13% ( p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD ( p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% ( p = 0.273) and 49% vs 35% ( p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

Introduction Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed. Areas covered The review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells. Expert opinion The development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

A survey within hematopoietic stem cell transplant (HSCT) centers of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) was performed in order to describe current antiemetic prophylaxis in patients undergoing HSCT. The multicenter survey was performed by a questionnaire, covering the main areas on chemotherapy-induced nausea and vomiting (CINV): antiemetic prophylaxis guidelines used, antiemetic prophylaxis in different conditioning regimens, and methods of CINV evaluation. The survey was carried out in November 2016, and it was repeated 6 months after the publication of the Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) specific guidelines on antiemetic prophylaxis in HSCT. The results show a remarkable heterogeneity of prophylaxis among the various centers and a significant difference between the guidelines and the clinical practice. In the main conditioning regimens, the combination of a serotonin3 receptor antagonist (5-HT3-RA) with dexamethasone and neurokin1 receptor antagonist (NK1-RA), as recommended by MASCC/ESMO guidelines, increased from 0 to 15% (before the publication of the guidelines) to 9-30% (after the publication of the guidelines). This study shows a lack of compliance with specific antiemetic guidelines, resulting mainly in under-prophylaxis. Concerted strategies are required to improve the current CINV prophylaxis, to draft shared common guidelines, and to increase the knowledge and the adherence to the current recommendations for CINV prophylaxis in the specific field of HSCT.

PURPOSE: Cyclophosphamide (CY) in a dose of 2-4 g/m(2) is widely used for hemopoietic progenitor stem cells mobilization. CY administration is associated with several adverse effects, including chemotherapy-induced nausea and vomiting (CINV). This study aimed to evaluate the efficacy and tolerability of granisetron transdermal system (GTDS) plus dexamethasone in the management of CINV in MM patients undergoing chemo-mobilization with CY. METHODS: In this single-center, prospective, observational, real world study, GTDS plus dexamethasone was administered to MM patients receiving chemo-mobilization based on CY 2 g/m2 plus G-CSF in an outpatient setting. The rate of complete response was evaluated as the main outcome. Other outcomes were rate of complete control of CINV, incidence of nausea/vomiting of any grade and safety. RESULTS: A total of 88 patients were enrolled. A complete response was achieved in 45.5 % of patients; among them, 39.77 % attained complete control of CINV. Nausea and vomiting never occurred in 34.1 % and 45.5 % of patients, respectively. No episodes of grade 3-4 nausea and/or vomiting were documented. GTDS was safe and well tolerated. CONCLUSION: In real world, GTDS provided an innovative, effective, and well-tolerated control of CINV in MM patients after chemo-mobilization with CY. The study found out effectiveness of a non-invasive delivery system of antiemetic.

Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT.

The application of different models of autologous stem-cell transplantation (ASCT) in multiple myeloma has demonstrated the feasibility and safety of outpatient-based programs of care. Although several systematic reviews have evaluated the burden of caregivers, only a few studies have included outpatient ASCT. We found that an outpatient model neither improves nor impairs the caregivers' burden. Background: The application of different models of autologous stem-cell transplantation (ASCT) in multiple myeloma has demonstrated the feasibility and safety of outpatient-based programs of care. Although several systematic reviews have evaluated the burden of caregivers, only a few studies have included outpatient ASCT. Patients and Methods: The feelings of lack of family support, daily activities, and general health were compared between caregivers of 2 groups of patients with multiple myeloma who underwent inpatient (n = 71) or outpatient (n = 25) ASCT. Results: The 3 features did not significantly differ between the 2 study groups at baseline, before, and 3 months after ASCT. Multivariate modeling showed that the baseline values were significantly related to the changes in study outcomes independent of patient and caregiver characteristics. Other correlates were caregivers' work and patient age for impact on daily activities and disease burden across time for impact on general health (all P < .05). Conclusion: The outpatient model neither improves nor impairs global caregivers' burden compared to standard ASCT care. Further research is needed to confirm this observation and to better assess the burden and quality of life of caregivers and their influence on patient outcomes and quality of life. (C) 2020 Elsevier Inc. All rights reserved.

Donor selection contributes to improve clinical outcomes of T-cell-replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.

A longitudinal, prospective, observational, single-center cohort study on healthy donors was designed to identify predictors of CD34+ cell mobilization on day 4 after granulocyte colony-stimulating factor (G-CSF) administration. As potential predictors of mobilization, age, sex, body weight, height, blood volume, WBC count, peripheral blood (PB) mononuclear cell count, platelet (Plt) count, and hematocrit and hemoglobin levels were considered. Two different evaluations of CD34+ cell counts were determined for each donor: baseline (before G-CSF administration) and in PB on day 4 after G-CSF administration. One hundred twenty-two consecutive healthy donors with a median age of 47.5 years were enrolled. The median value of CD34+ on day 4 was 43 cells/µL (interquartile range, 23 to 68), and 81.1% of donors had ≥20 cells/µL. Basal WBC count, Plt count, and CD34+ were significantly higher for the subjects with CD34+ levels over median values on day 4. A multivariate quartile regression analysis, adjusted by sex, age, basal CD34+, and basal Plt count, showed a progressively stronger relationship between baseline CD34+ and Plt levels and the CD34+ levels on day 4. The basal CD34+ cut-off level to predict the levels of CD34+ on day 4 was either ≤2 cells/μL or ≥3 cells/μL and that of basal Plt count was ≤229 × 109/L or ≥230 × 109/L, respectively, to determine whether mobilization therapy should or should not be attempted. PB stem cell mobilization with G-CSF was highly effective on day 4, and herein we describe a model for predicting the probability of performing PB stem cell collection after a short course of G-CSF.

Background: FDA designated ibrutinib as a breakthrough therapy in Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL). Nevertheless, patients who progress under ibrutinib still have a poor prognosis. In this setting, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could induce long-term disease control.Areas covered: The purpose of the present review is to provide information on the efficacy of ibrutinib when administered before and after allo-HSCT for CLL and MCL. Moreover, we will focus on the current role of ibrutinib for chronic GVHD.Expert opinion: Ibrutinib as bridge to allo-HSCT does not appear to affect the safety of the treatment in patients with CLL and MCL. Current evidence support further evaluation of ibrutinib for the treatment of relapsed CLL and MCL after allo-HSCT. In this setting, ibrutinib should be not only highly efficient on CLL and MCL cells but might also have the ability to enhance the activity of donor T cells. Chronic GVHD is the most common long-term complication following allo-HSCT. Results from a phase 2 clinical trial culminated in the FDA-approval of ibrutinib as second-line therapy of steroid-refractory or steroid-resistant chronic GVHD. A randomized, controlled trial in patients with chronic GVHD should be performed.

Introduction: Management of multiple myeloma (MM) has improved over recent years. Health-related quality of life (HRQoL) data is becoming increasingly important, owing to improved survival outcomes. Areas covered: The authors performed an expert review of the literature to identify evidence-based data available on HRQoL in frontline and relapsed/refractory MM (RRMM) patients. Expert opinion: De-novo patients should be informed that the HRQoL is expected to improve during first-line treatment with different degrees of possible deterioration during the first cycles. Achievement of a maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, HRQoL, and patient preferences. The same degree of improvement in HRQoL cannot be expected during conventional relapse treatments, where patients should be prepared only for stabilization of HRQoL. However, focusing attention only on measures such as toxicity may provide just a partial view of overall treatment effectiveness. Nonetheless, the authors believe the added value of taking into consideration the patient's perspectives and the importance of patient-reported outcomes in the evaluation of treatment effects should be considered mandatory. The incorporation of quality of life assessment into clinical and research practice has the potential of improving treatment outcomes.