Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Long-Term Efficacy of Erythropoiesis-Stimulating Agents in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Multicenter Real-Life Data

Objective: This study was undertaken to evaluate the long-term clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndrome (MDS) in a real-life setting. Materials and Methods: A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion needs were recorded before treatment and at 12 months, 24 months, 36 months, and 48 months of treatment. Results: At the 36-month (p=0.025) and 48-month (p=0.022) visits, epoetin alfa yielded significantly higher hemoglobin levels compared to darbepoetin alfa. Transfusion needs were also significantly lower with epoetin alfa compared to darbepoetin alfa at 24 months (p=0.012) and in the low-risk group compared to the intermediate-risk group at 24 months (p=0.018), 36 months (p=0.025), and 48 months (p<0.001). Treatment response rates at the 24-month, 36-month, and 48-month visits in the epoetin alfa (43.0%, 33.6%, and 27.1%), darbepoetin alfa (29.9%, 22.7%, and 16.5%), low-risk (39.3%, 30.0%, and 26.0%), and intermediate-risk (29.6%, 24.1%, and 11.1%) groups were lower than those obtained at 12 months, and the values differed significantly for the 36-month and 48-month visits with values ranging from p<0.05 to p<0.001. Conclusion: This real-life long-term ESA extension study investigated the clinical efficacy of epoetin alfa and darbepoetin alfa for up to 48 months, revealing that treatment efficacy reached a plateau starting from the 24th month of therapy with a continuing decrease in treatment response rates regardless of treatment type, risk status, or gender. Nonetheless, significantly higher hemoglobin levels and marked improvement in transfusion needs were evident in epoetin-treated patients compared to darbepoetin-treated patients and in the low-risk group compared to the intermediate-risk group.

The Clinical Efficacy of Epoetin Alfa and Darbepoetin Alfa in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Retrospective Multi-center Real-Life Study.

This study aimed to evaluate the clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndromes (MDS) in the real-life setting. A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion need were recorded before and during 12-month treatment. Hemoglobin levels were significantly higher at each follow up visit when compared to baseline levels in both epoetin alfa (mean ± SD 8.68 ± 1.0 g/dL at baseline vs. 9.83 ± 1.45, 9.99 ± 1.55, 10.24 ± 1.77 and 10.2 ± 1.5 g/dL, respectively) and darbepoetin alfa (8.83 ± 1.09 g/dL at baseline vs. 9.62 ± 1.37, 9.78 ± 1.49, 9.9 ± 1.39 and 10.1 ± 1.5 g/dL, respectively) groups (p < 0.001 for each). Transfusion need significantly decreased from baseline at each study visit in the epoetin alfa group (p < 0.001) and only at the 12th month visit (p < 0.001) in the darbepoetin alfa group. Hemoglobin levels or transfusion need was similar between treatment groups. Overall, 12-month response rate was 58.1% for epoetin alfa and 41.9% for darbepoetin alfa, with no significant difference between treatment groups, whereas higher response rate was noted within the first three months (62.7%) compared to next 9 months (ranged 44.4-60%) of treatment in the epoetin alfa group (p ranged 0.002 to < 0.001). This real-life retrospective study revealed similar efficacy of epoetin alfa and darbepoetin alfa among low risk or intermediate-1 risk MDS patients with no difference in treatment response between treatment groups, whereas a likelihood of earlier treatment response in the epoetin alfa group. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01458-1.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Original Versus Generic Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Comparison of Efficacy and Adverse Events

Objective: Lenalidomide is an effective immunomodulatory derivative drug used in the treatment of multiple myeloma (MM). It is available in original and generic forms in Turkey, but there is no clinical study that has compared the effectiveness and adverse events (AEs) of the generic and original forms of lenalidomide. We compared the effectivity and AEs of generic and original lenalidomide in patients with relapsed/refractory MM (RRMM). Materials and Methods: Patients with RRMM using original or generic lenalidomide were evaluated retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease, and progressive disease rates and hematologic and nonhematologic AEs were evaluated in these RRMM patients. The results were described as numbers, frequencies, and percentages and were analyzed using PASW 19.0 for Windows with chi-square and Fisher exact tests. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. The OR rate was 67.2% for patients using original lenalidomide and 60.4% for those on generic lenalidomide. CR and VGPR rates were 14.5% and 45.4% in the original group while the CR and VGPR rates were 20.9% and 18.6%, respectively, in patients using generic lenalidomide. Hematologic AEs were similar in the two groups while some nonhematologic AEs were less common in the original lenalidomide group than the generic group. Only pyrexia as a grade 3-4 AE was more common in the original lenalidomide than the generic lenalidomide group. Conclusion: This study showed that the generic form of lenalidomide has similar efficacy with the original form of lenalidomide in the treatment of RRMM. The AEs of original lenalidomide were generally fewer than those of generic lenalidomide. Further studies involving a larger number of patients with RRMM would be useful for comparing the efficacy and AEs of original and generic lenalidomide.

Cholesterol Levels in Patients with Chronic Lymphocytic Leukemia.

Low cholesterol levels may be accompanied by solid tumors or hematological malignancies such as multiple myeloma. Decreased cholesterol levels have been reported in some experimental studies about chronic lymphocytic leukemia (CLL). It may be associated with tumoral cell metabolism. Herein, we examine blood lipid profiles of patients with newly diagnosed CLL (284 male, 276 female, mean age 64 ± 11 years) as defined by National Cancer Institute criteria. The control group consisted of 71 healthy subjects with mean age 55 ± 9 years (28 male, 43 females). 60% of patients with Binet A, while 25% were Binet C. Decreased levels of total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) were observed in patients with CLL than control group (p < 0,001). There was no statistical significance between CLL and control group for triglycerides (TG) and very low density lipoprotein (VLDL), also between HDL-C, VLDL, TG and grades. Cholesterol may metabolized by abnormal lymphocytes in CLL patients.

Pesg PNH diagnosis, follow-up and treatment guidelines.

PNH Education and Study Group (PESG) have been established in December 2013 as a non-profit, independent, medical organization www.pesg.org. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a multi-systemic disease that should be treated with a multidisciplinary approach. Patients may apply to the clinics other than the hematology due to variability and diversity of clinical findings which lower the rate of diagnosis due to low awareness about PNH. PNH might be overlooked and diagnosis might be delayed. Regarding these, PESG was established with the collaboration of Immunology, Cardiology, Thorax Diseases (Pulmonology), Neurology, Gastroenterology, General Surgery and Urology specialists in addition to hematologists dealing with PNH. The PESG study group aims to increase the awareness about PNH, including training activities about PNH, strengthening the relations between clinics and planning of clinical studies as a goal. It is the first professional organization focusing on PNH, in Turkey.In this guideline, we want to facilitate the diagnosis attributes of physicians from all specializations that deal with PNH and its systemic complications. One can perceive this as a tailor made guideline of international guidelines but not a compilation.