Severe Liver Dysfunction after Donor Lymphocyte Infusion for Relapsed Multiple Myeloma.

Donor lymphocyte infusion (DLI) is performed to augment an anti-tumor immune response or ensure donor stem cells remain engrafted following allogeneic stem cell transplantation but may induce graft-versus-host disease (GVHD) involving skin, intestine, and liver. Although hepatic involvement of GVHD can manifest as mild to severe hepatitis, few reports have mentioned acute severe liver dysfunction with encephalopathy. We experienced a case of acute severe liver dysfunction with semicoma after DLI in a patient with relapsed multiple myeloma following allogeneic stem cell transplantation, in whom chronic viral hepatitis B had been suppressed by antiviral treatment. The patient recovered after high-dose glucocorticoid administration based on an assessment of hepatic GVHD. Clinicians should be aware of the possibility of this catastrophic hepatic complication after DLI in hematologic disorders.

Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial.

Potential synergism between Bruton's tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142).

Nation-Wide Retrospective Analysis of Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma: A Study from Korean Multiple Myeloma Working Party (KMM1913).

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response (sCR) plus CR rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3 and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0, 88.9, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion: AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Outcome of Multiple Myeloma Patients With Hepatitis B Surface Antigen: Korean Multiple Myeloma Working Party 2103 Study.

BACKGROUND: Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS: We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS: The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION: Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea.

PURPOSE: Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. MATERIALS AND METHODS: Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. RESULTS: The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. CONCLUSION: In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Comparison of first-line treatment with CHOP versus ICED in patients with peripheral T-cell lymphoma eligible for upfront autologous stem cell transplantation.

Introduction: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods: We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results: Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion: In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.

Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015).

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.

Real-world data of long-term survival in patients with T-cell lymphoma who underwent stem cell transplantation.

This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.

Incidence and risk factors of opportunistic infections after autologous stem cell transplantation: a nationwide, population-based cohort study in Korea.

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection.

A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

INTRODUCTION: This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS: We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS: No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). DISCUSSION: Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).

Results of Multicenter Phase II Study With Imatinib Mesylate in Allogeneic Recipients With Steroid-Refractory Chronic GVHD.

In this multicenter phase II study, we evaluated the safety and efficacy of imatinib in patients with steroid-resistant chronic graft-versus-host disease (cGVHD) and evaluated the quality of life (QOL) of the enrolled patients using the Short Form 36 (SF-36) health survey questionnaire. Thirty-six patients who were diagnosed with steroid-refractory cGVHD and treated with imatinib between March 2013 and February 2019 received 100 mg/day of imatinib for 2 weeks. Depending on the patient's condition and investigator's decision, the imatinib dose was allowed to be increased by 100 mg every 2 weeks up to 400 mg/day. Patients who achieved stable disease (SD), partial remission (PR), and complete remission (CR) at 3-month response evaluations continued imatinib for up to 6 months. The majority of the patients had multi-organ cGVHD, with skin (63.9%), lungs (44.4%), mouth (38.9%), and eyes (38.9%) as the most common sites. The overall response rate was 58.3%, including 3 and 18 patients with CR and PR, respectively, and an overall decline in National Institutes of Health (NIH) severity scores was observed at study completion in the absence of significant adverse effects. The overall response rates were 70.5%, 66.7%, 34.8%, and 25% in patients with gastrointestinal, liver, skin, and lung cGVHD, respectively. Factors representing emotional well-being were significantly improved based on the patient-reported QOL evaluation using SF-36. The effect of imatinib on steroid tapering, which was notable in responders, was also present in 50% of those who achieved SD without worsening cGVHD. Imatinib exhibited therapeutic efficacy in steroid-refractory and steroid-dependent cGVHD with tolerable toxicity.Clinical Trial Registration: KCT0006785.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Influence of creatinine levels on survival in patients with veno-occlusive disease treated with defibrotide.

BACKGROUND/AIMS: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. METHODS: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. RESULTS: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. CONCLUSION: The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

Metal-Organic Frameworks Reinforce the Carbon Nanotube Sponge-Derived Robust Three-Dimensional Sulfur Host for Lithium-Sulfur Batteries.

Sulfur is a prospective material for next-generation batteries with high theoretical capacity, but its drawbacks hinder its commercialization. To overcome the low conductivity of natural sulfur and the shuttle effect of lithium polysulfide, the study proposes a novel sulfur film coated with three-dimensional nitrogen and cobalt-codoped polyhedral carbon wrapped on a multiwalled carbon nanotube sponge (3D-S@NCoCPC sponge) composite as a high-performance cathode material for rechargeable lithium-sulfur batteries. The interconnected conductive carbon network with abundant pores provides more room for the homogeneous distribution of sulfur within the composite and creates a favorable pathway for electrolyte permeability and lithium-ion diffusion. Moreover, the strong interaction between cobalt and lithium polysulfides leads to efficient suppression of the shuttle effect. In addition, the homogeneous distribution of sulfur and cobalt within the composite enhances electronic transfer for the conversion reaction of sulfur. As expected, the cathode with a high sulfur content of 77.5 wt % in the composite achieved a high initial discharge capacity of 1192 mA h g-1 and high Coulombic efficiency of 99.98% after 100 cycles at 100 mA g-1 current density. Stable performance was achieved with 92.9% capacity retention after 200 cycles at 1000 mA/g current density.

Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma.

BACKGROUND: We investigated whether distancemax, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). METHODS: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. RESULTS: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P <0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594‒4.822; P =0.003], short distancemax (PFS: HR, 0.170; 95% CI, 0.071‒0.410; P <0.001; OS: HR, 0.142; 95% CI, 0.050‒0.402; P < 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P <0.001; OS: HR, 0.193; 95% CI, 0.087‒0.429; P <0.001) had an independent predictive value for PFS and OS. CONCLUSION: The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.

Clinical Impact of Extranodal Metabolic Tumor Volume in 240 Diffuse Large B cell Lymphoma Patients with Extranodal Involvement.

The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.

Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone.

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival.

Comprehensive pulmonary rehabilitation in patients with bronchiolitis obliterans syndrome: A case series.

Chronic graft-versus-host disease (GVHD) is a significant complication of allogeneic hematopoietic stem cell transplantation, affecting 30%-70% of transplant recipients. One of the most challenging manifestations of chronic pulmonary GVHD is bronchiolitis obliterans syndrome (BOS), a rare and difficult-to-diagnose disease associated with a high mortality rate. BOS results in progressive circumferential fibrosis and, ultimately, cicatrization of the small terminal airways, manifesting as new fixed airflow obstruction. Although BOS patients are typically treated with immunosuppressive agents, there is no strong evidence that any specific therapies are effective in improving long-term outcomes. Thus, the mortality rate remains high. Therefore, there is an increasing need for additional therapies, including pulmonary rehabilitation (PR), in patients with BOS. PR is an evidence-based and comprehensive intervention for patients with chronic obstructive lung disease aimed at alleviating respiratory symptoms and optimizing functional capacity. This present case series demonstrates that comprehensive PR may also improve exercise tolerance and dyspnea in patients with BOS.

Pomalidomide, cyclophosphamide, and dexamethasone for elderly patients with relapsed and refractory multiple myeloma: A study of the Korean Multiple Myeloma Working Party (KMMWP-164 study).

Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality.