The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients.

BACKGROUND: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab. OBJECTIVE: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment. METHODS: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment. RESULTS: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/µL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen. CONCLUSION: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

Consolidation with 90 Yttrium-ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma.

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90 Yttrium-ibritumomab tiuxetan (90 Y-IT) after re-induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re-induction therapy with BR was administered every 4 weeks up to 4-6 cycles. If patients achieved at least partial response, 90 Y-IT was administered as consolidation therapy. The primary endpoint was 2-year progression-free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90 Y-IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2-year PFS rate after the consolidation among the 22 patients receiving 90 Y-IT was 59% (95% confidence interval [CI], 38%-77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2-year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2-year overall survival after the consolidation was 95% (95% CI, 74%-99%). In conclusion, in a subset of patients with previously treated FL, 90 Y-IT consolidation after BR re-induction conferred a durable remission, indicating that consolidation therapy using 90 Y-IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).

Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma.

The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum - minimum values of M protein during the 90 days before the start of LEN) divided by M-protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non-IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression-free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.

Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis.

OBJECTIVES: This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). METHODS: We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. RESULT: At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. CONCLUSION: This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.

Chronic active EBV infection in refractory enteritis with longitudinal ulcers with a cobblestone appearance: an autopsied case report.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is defined as Epstein-Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn's disease (CD) based on ileal ulcers and clinical symptoms of enteritis. CASE PRESENTATION: A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years. CONCLUSION: Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

[Treatment strategy for patients with thrombotic thrombocytopenic purpura].

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially life-threatening disease that is characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and ischemic organ damage resulting from the formation of platelet-rich thrombi in the microvasculature. It is especially related to a severe deficiency of ADAMTS13, the specific von Willebrand factor-cleaving protease. Thus, <10% of the normal activity of ADAMTS13 is an essential diagnostic marker for establishing a diagnosis of TTP. TTP can be of congenital form that is termed the Upshaw-Schulman syndrome (USS) that is caused by genetic abnormality of ADAMTS13 and acquired form that is caused by autoantibodies against ADAMTS13. The congenital form is treated with the infusion of fresh frozen plasma, and the treatment of the acquired form involves plasma exchange combined with immunosuppressive therapy that uses corticosteroids and rituximab. Recently, the efficacy and safety of new drugs caplacizumab, single-domain antibody against ADAMTS13, and recombinant ADAMTS13 products have been reported in large-scale clinical trials conducted in other countries. These results suggested the better outcome in the treatment for the patients with TTP in the near future.

Novel aptamer to von Willebrand factor A1 domain (TAGX-0004) shows total inhibition of thrombus formation superior to ARC1779 and comparable to caplacizumab.

von Willebrand factor (VWF) is a blood glycoprotein that plays an important role in platelet thrombus formation through interaction between its A1 domain and platelet glycoprotein Ib. ARC1779, an aptamer to the VWF A1 domain, was evaluated in a clinical trial for acquired thrombotic thrombocytopenic purpura (aTTP). Subsequently, caplacizumab, an anti-VWF A1 domain nanobody, was approved for aTTP in Europe and the United States. We recently developed a novel DNA aptamer, TAGX-0004, to the VWF A1 domain; it contains an artificial base and demonstrates high affinity for VWF. To compare the effects of these three agents on VWF A1, their ability to inhibit ristocetin- or botrocetin-induced platelet aggregation under static conditions was analyzed, and the inhibition of thrombus formation under high shear stress was investigated in a microchip flow chamber system. In both assays, TAGX-0004 showed stronger inhibition than ARC1779, and had comparable inhibitory effects to caplacizumab. The binding sites of TAGX-0004 and ARC1779 were analyzed with surface plasmon resonance performed using alanine scanning mutagenesis of the VWF A1 domain. An electrophoretic mobility shift assay showed that R1395 and R1399 in the A1 domain bound to both aptamers. R1287, K1362, and R1392 contributed to ARC1779 binding, and F1366 was essential for TAGX-0004 binding. Surface plasmon resonance analysis of the binding sites of caplacizumab identified five amino acids in the VWF A1 domain (K1362, R1392, R1395, R1399, and K1406). These results suggested that TAGX-0004 possessed better pharmacological properties than caplacizumab in vitro and might be similarly promising for aTTP treatment.

The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017.

Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype-phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment for a study which aimed to improve the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS13 activity with emphasis on the recurring ADAMTS13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS13 activity (≤10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS13 mutations on both alleles. By the end of 2017, 123 confirmed patients had been enrolled from Europe (n=55), Asia (n=52, 90% from Japan), the Americas (n=14), and Africa (n=2). First recognized disease manifestation occurred from around birth up to the age of 70 years. Of the 98 different ADAMTS13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS13 c.4143_4144dupA with overt disease onset at < 3 months of age (50% vs 37%), despite the fact that ADAMTS13 activity was <1% in 18 of 20 homozygous, but in only 8 of 14 compound heterozygous carriers. An evaluation of overt disease onset in all patients with an available sensitive ADAMTS13 activity assay (n=97) shows that residual ADAMTS13 activity is not the only determinant of age at first disease manifestation. Registered at clinicaltrials.gov identifier NCT01257269.

SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.

Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. ß/A4(Aß) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aß deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders.

Initial treatment strategy for patients newly diagnosed with multiple myeloma.

In Japan, the latest trends in induction therapy for patients newly diagnosed with multiple myeloma are multi-drug combinations, including bortezomib, lenalidomide, and thalidomide. Patients <65 years old and those <70 years old who have normal cardiac and lung functions without any serious complications are good candidates for high-dose L-PAM with autologous stem cell transplantation. For successful stem cell collection, anti-cancer drugs that have a negative impact on stem cell mobilization are usually excluded from induction therapies. It has been reported that bortezomib and thalidomide do not affect mobilization of stem cells; however, extended exposure to lenalidomide may have a potential risk of poor mobilization. Under these circumstances, PAD, VTD, VCD, and RVD are recommended as first induction therapies for transplant-eligible patients. On the other hand, two- or three-drug combinations are effective as induction therapies for transplant-ineligible patients >65-70 years old and <65 years old with serious complications or insufficiencies of cardiac or lung functions as well as for any patients who refuse transplantation strategy. For these patients, VMP, MPT, and Rd are usually recommended. For elderly patients >75 years old, it is important that the dosage of each drug be properly reduced according to the frailty of the patient.

Second primary malignancies among patients with myeloma-related-diseases in the KMF database.

The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed.

Successful treatment of an elderly frail patient with acquired idiopathic thrombotic thrombocytopenic purpura under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers.

A 68-year-old woman was admitted to the regional hospital because of hemolytic anemia, thrombocytopenia, and neurological abnormalities including unconsciousness. One week before admission, she suffered from diarrhea and subsequently passed out and hit her face on the ground. She was suspected of having TTP and was transferred to our hospital. We performed the assays of ADAMTS13 activity and anti-ADAMTS13 antibody titers, and confirmed the diagnosis of acquired idiopathic TTP with total deficiency of ADAMTS13 activity with its inhibitor. She was initially treated with plasma exchange combined with corticosteroids, however, we were forced to substitute plasma exchange with fresh frozen plasma infusion due to procedure-associated complications. The infusion of fresh frozen plasma was known as less effective and more likely to boost inhibitor titers compared to plasma exchange. In this circumstance, we could successfully switch the plasma therapy under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers which precisely revealed the disease status of TTP in our patient, and eventually she achieved complete remission with normal level of ADAMTS13 activity and no inhibitor. Our experience suggested that the measurement of ADAMTS13 activity and inhibitor titer might be valuable not only for making the diagnosis but also for guiding treatment decisions by precise evaluating of disease status in patients with the acquired form of TTP.

[Proteasome inhibitor].

The ubiquitin-proteasome system plays an essential role in degradation of eukaryotic intracellular protein, including cell cycle regulation, cell growth and proliferation, and survival. Cancer cells generally have higher level of proteasome activity compared with normal cells, suggesting proteasome inhibition could be therapeutic target in oncology. Bortezomib, the first proteasome inhibitor introduced into the clinic, is approved for the treatment of patients with multiple myeloma (MM). Although it was approved as single agent in the relapsed setting, bortezomib is now predominantly used in combination with conventional and novel targeted agents because bortezomib has demonstrated additive and synergistic activity in preclinical studies. Recently, several second-generation proteasome inhibitors, such as carfilzomib and MLN9708, have been developed and entered into clinical trials. These agents were investigated in frontline MM in combination with lenalidomide and low-dose dexamethasone. These studies demonstrated positive efficacy and safety, and it is expected that they will be approved in near future.

Persistent ADAMTS13 inhibitor delays recovery of ADAMTS13 activity in caplacizumab-treated Japanese patients with iTTP.

ABSTRACT: For patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), caplacizumab, a nanobody against von Willebrand factor A1 domain, has become crucial. Delayed normalization of ADAMTS13 activity during caplacizumab therapy has been identified. In a retrospective analysis, we compared platelet count, ADAMTS13 activity, its inhibitor, and anti-ADAMTS13 immunoglobulin G (IgG) levels in acute iTTP cases treated with caplacizumab (n = 14) or without it (n = 16). The median time from initial therapeutic plasma exchange (TPE) to the first rituximab administration was 12 days in the caplacizumab group (n = 11) and 10 days in the group without caplacizumab (n = 13). We evaluated ADAMTS13-related parameters at onset and once a week until day 28 after the first TPE. The number of days until the platelet counts reached ≥150 × 109/L was significantly shorter in the caplacizumab group than in the non-caplacizumab group. The median ADAMTS13 activity levels on days 14, 21, and 28 were significantly lower in the caplacizumab group. The median titers of the ADAMTS13 inhibitor and anti-ADAMTS13 IgG on the same days were significantly higher in the caplacizumab group. Furthermore, the median number of days from the first TPE until finally achieving an ADAMTS13 activity of ≥10% was significantly longer in the caplacizumab group than in the non-caplacizumab group (42 vs 23 days, P = .014). We observed delayed ADAMTS13 activity recovery and continued inhibitor and anti-ADAMTS13 IgG detection in patients with acute iTTP on caplacizumab, possibly because of the decreased number of TPEs and delayed frontline rituximab.

Patient with Adult T-cell Leukemia and Lung Infection caused by Mycobacterium abscessus: Successful Treatment with Intensive Chemotherapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report.

A 63-year-old woman with adult T-cell leukemia (ATL) lymphomatous type developed a mild dry cough. Computed tomography revealed lung lesions with a tree-in-bud appearance during intensive chemotherapy. Antibodies against Mycobacterium avium complex were positive. Bronchoalveolar lavage culture showed growth of M. abscessus complex. Finally, M. abscessus subsp. massiliense was also identified. Sequential use of antimicrobials, including macrolides, was introduced during intensive chemotherapy, and the patient successfully underwent allogeneic hematopoietic stem cell transplantation (AHSCT). This is the first case report of a patient with ATL complicated by M. massiliense lung infection, who was successfully treated with haploidentical AHSCT using various combinations of antimicrobials.

Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023.

Thrombotic thrombocytopenic purpura (TTP) can rapidly become a life-threatening condition, and the importance of its appropriate diagnosis and treatment cannot be overstated. Until recently, TTP has mainly been diagnosed by clinical findings such as thrombocytopenia and hemolytic anemia. In addition to these clinical findings, however, reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% has become internationally accepted as a diagnostic criterion for TTP. TTP is classified as immune-mediated TTP (iTTP) if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital TTP (cTTP) if ADAMTS13 gene abnormalities are detected. Fresh frozen plasma (FFP) transfusion is performed in patients with cTTP to supplement ADAMTS13. Plasma exchange therapy using FFP is conducted in patients with iTTP to supplement ADAMTS13 and to remove both anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. To suppress autoantibody production, corticosteroid therapy is administered in conjunction with plasma exchange. The monoclonal anti-CD-20 antibody rituximab is effective in patients with iTTP. In addition, caplacizumab, an anti-VWF A1 domain nanobody, has a novel mechanism of action, involving direct inhibition of platelet glycoprotein Ib-VWF binding. The recommended first-line treatments of iTTP in Japan are plasma exchange and corticosteroids, as well as caplacizumab.

Real-world data on induction therapy in patients with transplant-ineligible newly diagnosed multiple myeloma: retrospective analysis of 598 cases from Kansai Myeloma Forum.

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22). Younger patients tended to receive VRd or VCD, whereas the regimen with the highest median patient age was Rd. More than three-quarters of patients in the Rd group received a reduced dose of lenalidomide. The Rd and VRd groups had a relatively high incidence of infection and skin complications, and the VMP group had the highest incidence of peripheral neuropathy. Overall response rate did not differ significantly between regimens. Multivariate analysis in all patients revealed several poor prognostic factors, such as poor performance status. Novel drug-containing regimens for newly diagnosed MM showed a durable response with manageable AEs in the real-world setting.

Efficacy of elotuzumab for multiple myeloma in reference to lymphocyte counts and kappa/lambda ratio or B2 microglobulin.

Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower ß2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/µL), non-deviated κ/λ ratio (0.1-10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/µL and 1 point for < 1400/µL) and κ/λ ratio (0 points for 0.1-10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system.