Chemokine Receptor 4-Targeted PET/CT with [68Ga]pentixather in Newly Diagnosed Multiple Myeloma: a Comparative Study with [68Ga]pentixafor PET/CT.

PURPOSE: This study aimed to compare the detection rate of [68Ga]pentixather PET/CT and [68Ga]pentixafor PET/CT in newly diagnosed multiple myeloma (NDMM) patients, and to explore the value of [68Ga]pentixather PET/CT for tumor load assessment. METHODS: Nineteen NDMM Patients were prospectively recruited and underwent both [68Ga]pentixather PET/CT and [68Ga]pentixafor PET/CT. A positive PET scan was defined as the presence of PET-positive focal bone lesions, paraskeletal disease, extramedullary plasmacytoma, or diffuse bone marrow uptake. Lesion numbers, SUVmax and PET-related tumor burden values were compared. The correlations between PET-related tumor burden and clinical risk stratification were analyzed. RESULTS: [68Ga]pentixather PET/CT showed a tendency of higher positive rate compared with [68Ga]pentixafor PET/CT [94.7% (18/19) vs. 78.9% (15/19), p > 0.05]. Among 14 patients with 151 matched focal bone lesions, [68Ga]pentixather PET detected more or equal number of lesions in 13 patients, and demonstrated higher uptake value than 68 Ga-pentixafor PET [SUVmax, 16.8 (9.0, 23.8) vs. 13.4 (6.5, 20.4), p < 0.001]. For PET related-tumor burden, positive correlations of total bone marrow uptake (TBmU) (r = 0.9540, p < 0.0001) and SUVmean of total bone marrow (r = 0.9632, p < 0.0001) in two PET scans were observed. Higher TBmU [7864.9 (5549.2, 11,616.2) vs. 5383.4(4102.7, 11,041.8), p < 0.001], SUVmean of total bone marrow [1.4 (1.1, 2.2) vs. 1.1 (0.7, 2.1), p < 0.001] were demonstrated on [68Ga]pentixather PET than [68Ga]pentixafor PET. And the level of TBmU in [68Ga]pentixather PET and [68Ga]pentixafor PET were both elevated in Durie-Salmon Staging (DSS) III than DSS I (p < 0.01). CONCLUSIONS: [68Ga]pentixather PET/CT performed a non-inferior capability for tumor detection compared to [68Ga]pentixafor PET/CT in NDMM patients. [68Ga]pentixather PET/CT can assess tumor load in MM patients and depict a significantly higher PET-related total tumor burden than [68Ga]pentixafor PET/CT.

Vaginal involvement as a rare extranodal manifestation in advanced-stage follicular lymphoma: a case report and literature review.

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina.

MYC translocation is a valuable marker for the development and relapse of extramedullary disease in multiple myeloma.

OBJECTIVE: To study the cytogenetic characteristics of extramedullary disease (EMD) in patients with multiple myeloma (MM) and their impact on prognosis. METHODS: Patients with newly diagnosed MM (NDMM) at Peking Union Medical College Hospital (Beijing, China) between June 2007 and December 2019 were recruited for this study. Demographic information, clinical data, fluorescence in situ hybridization (FISH) results of marrow and tissue samples, and survival outcome data were collected. RESULTS: A total of 439 patients with NDMM were divided into those without EMD (non-EMD, n = 339), those with EMD with primary paraosseous plasmacytoma (pEMD-B, n = 48), those with primary EMD with soft-tissue involvement (pEMD-S, n = 33), and those with secondary EMD (sEMD, n = 19). The incidence of EMD was 18.5% (81/439) at diagnosis and 22.8% (100/439) throughout the disease course. Comparison of FISH results showed a higher proportion of RB1 deletion (n = 20; 60.0% vs. 20.0%, p = .013) and MYC translocation (n = 12; 44.4% vs. 12.5%, p = .041) in the extramedullary tissues than in the paired bone marrow samples. At diagnosis, the percentage of MYC translocations in the sEMD group was notably higher than that in the non-EMD group (55.6% vs. 15.5%, p = .012). The median overall survival (OS) of patients with pEMD-S (32 months) and sEMD (17 months) was significantly shorter (both p = .001) than that of non-EMD patients (60 months). CONCLUSION: Soft-tissue EMD can be considered a high-risk condition, even in the era of novel agents. MYC translocation can serve as a valuable marker that correlates with extramedullary spread and relapse in patients with MM and should be considered for inclusion in routine FISH panels in clinical practice.

Percutaneous vertebroplasty/kyphoplasty contributes to the improved outcome in patients with newly diagnosed multiple myeloma: A single center cohort study.

Objective: To evaluate the efficacy and prognosis of percutaneous vertebroplasty/kyphoplasty (PVP/PKP) in patients with newly diagnosed multiple myeloma (NDMM). Methods: Clinical data of NDMM patients who underwent PVP/PKP during front-line regimen at Peking Union Medical College Hospital from January 1, 2003, to June 30, 2023, were analyzed. Patients with comparable bone diseases not receiving orthopedic surgery were selected as controls. Visual analogue scale (VAS) score, progression-free survival (PFS), and overall survival (OS) were compared. Results: Baseline characteristics were matched between the surgical group (n = 51 with 56 surgeries) and non-surgical group (n = 102), including demographics, tumor load, International Staging System (ISS), bone diseases, cytogenetic abnormalities, first-line treatment, and autologous stem-cell transplantation (ASCT). Bone lesions for PVP/PKP were located at thoracic vertebrae (53.6 %, 30/56) or lumbosacral vertebrae (46.4 %, 26/56). The postoperative VAS score was significantly improved (2.25 ± 0.81 vs 5.92 ± 1.05, P < 0.001). The median follow-up time was 51[38-70] months. Kaplan-Meier survival analysis suggested that both PFS (37[17-89] vs 23[12-61] months, HR 0.648, 95 %CI 0.431-0.973, P = 0.047) and OS (not reached vs 66[28-NR] months, HR 0.519, 95 %CI 0.296-0.910, P = 0.045) were significantly prolonged in the surgical group. COX multivariate analysis suggested that PVP/PKP was an independent prognostic factor for PFS (P = 0.021, HR 0.589, 95 %CI 0.376-0.922) and OS (P = 0.038, HR 0.496, 95 %CI 0.255-0.963). Subgroup analysis confirmed that patients with ISS II/III or non-ASCT achieved better PFS and OS in the surgical group (PFS: P = 0.033, P = 0.040; OS: P = 0.024, P = 0.018 respectively), while similar survival outcome was observed in patients with ISS I or ASCT between two groups. Conclusion: For NDMM patients, not only does PVP/PKP alleviate bone pain, meanwhile, it improves the PFS and OS in advanced subpopulation or non-transplant myeloma patients, which suggests that shortening the gap from symptom onset to diagnosis by orthopedic surgery favors clinical prognosis.

Myc rearrangement redefines the stratification of high-risk multiple myeloma.

BACKGROUND: Myc rearrangement (Myc-R) is a controversial factor linked to adverse outcomes in newly diagnosed multiple myeloma (NDMM). AIMS: This study aimed to evaluate the impact of Myc-R on the prognosis of NDMM patients and its role in risk stratification compared with traditional high-risk cytogenetic abnormalities (HRCAs). MATERIALS & METHODS: A total of 417 NDMM patients enrolled from May 2009 to September 2022 were included. Fluorescence in situ hybridization (FISH) was used to detect Myc-R and other Myc abnormalities (Myc-OA). Median progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and log-rank tests. Multivariate Cox regression analysis was used to identify independent risk factors. RESULTS: Myc-R was identified in 13.7% of patients, while 14.6% had Myc-OA. Patients with Myc-R had significantly shorter median PFS (15.9 months) and OS (25.1 months) compared with those with Myc-OA (24.5 months PFS; 29.8 months OS) and Myc-negative (Myc-N) status (29.8 months PFS, 29.8 months OS). Myc-R was independently associated with worse PFS and OS compared to Myc-OA. Patients with Myc-R alone had inferior median PFS (15.9 months vs. 28.1 months, p = 0.032) and OS (25.1 months vs. 61.2 months, p = 0.04) compared to those with traditional single HRCA. DISCUSSION: The study suggests that traditional single HRCA may not significantly impact survival in NDMM patients. However, incorporating Myc rearrangement or traditional double/triple-hit HRCAs into the risk stratification model improves its predictive value, highlighting the importance of Myc rearrangement in risk assessment. CONCLUSION: Myc rearrangement is an independent adverse prognostic factor in NDMM. The incorporation of Myc rearrangement or multiple HRCAs into risk stratification models improves their prognostic value, providing a novel perspective on high-risk factors in NDMM.

Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.

Chemokine Receptor 4-Targeted PET/CT With 68 Ga-Pentixather Detects More Lesions Than 68 Ga-Pentixafor PET/CT in Multiple Myeloma.

ABSTRACT: An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68 Ga-pentixather and 68 Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68 Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68 Ga-pentixather PET/CT were higher than those on 68 Ga-pentixafor PET/CT. This suggests that 68 Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68 Ga-pentixafor PET/CT.

Prognostic Implications of Circulating Plasma Cell Percentage in Multiple Myeloma and Primary Plasma Cell Leukemia Defined by New Criteria.

INTRODUCTION: The definition of primary plasma cell leukemia (pPCL) has been revised from ≥20% to ≥5% circulating plasma cells (CPC). However, the precise prognosis associated with CPC remains controversial. This study aimed to investigate prognostic biomarkers for myeloma patients based on CPC presence. METHODS: A comprehensive analysis was conducted on 309 consecutive patients diagnosed with either multiple myeloma or pPCL, utilizing peripheral blood smears stained with Wright-Giemsa. RESULTS: Patients were grouped by CPC percentage: 0% (221, 71.5%), 1-4% (49, 15.9%), 5-19% (16, 5.2%), ≥20% (23, 7.4%). CPC >5% correlated with unfavorable characteristics, including anemia, renal dysfunction, and advanced International Staging System. Common cytogenetic abnormalities such as 1q21 amplification, 17p deletion, and Myc rearrangement were prevalent among CPC-positive patients. Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with CPC ≥5% (29.47 vs. 10.03 months; 64.10 vs. 12.30 months). Additionally, PFS and OS were shorter in CPC-positive patients without autologous hematopoietic stem cell transplantation (ASCT) and those with response < partial remission to the first-line regimen. Furthermore, an association emerged between soft tissue-related extramedullary disease and inferior PFS, while Myc rearrangement correlated with abbreviated OS. CONCLUSION: Biological characteristics displayed greater aggressiveness in patients with positive CPC, leading to significantly shorter PFS and OS. The presence of CPC, ASCT, and overall response rate were independent prognostic factors. While no new threshold for pPCL with CPCs is proposed, Myc rearrangements and CPC positivity could serve as ultra-high-risk factors for multiple myeloma.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Complete blood and urine paraprotein tests as response assessments in multiple myeloma patients treated with bortezomib, cyclophosphamide, and dexamethasone.

Background: This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018. Results: There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression-free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion: Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

Efficacy, safety, and survival findings after long-term follow-up of ZGJAK002: A phase 2 study comparing jaktinib at 100 mg twice daily (BID) and 200 mg once daily (QD) in patients with myelofibrosis.

Jaktinib, a novel JAK and ACVR1 inhibitor, has exhibited promising results in treating patients with myelofibrosis (MF). ZGJAK002 is a Phase 2 trial aimed to assess the efficacy and safety of jaktinib 100 mg BID (N = 66) and 200 mg QD (N = 52) in JAK inhibitor-naive patients with intermediate- or high-risk MF. We herein present the long-term data with a median follow-up of 30.7 months. At data cutoff, 30.3% of patients in 100 mg BID and 28.8% in 200 mg QD were still continuing their treatment. The 100 mg BID group displayed a numerically higher best spleen response compared with the 200 mg QD group (69.7% vs. 46.2%), with 50.4% from the BID and 51.2% from the QD group maintaining spleen responses over 120 weeks. The 36-month survival rates were 78.2% in BID and 73.6% in QD group. The tolerability of jaktinib remained well, and common grade ≥3 adverse drug reactions included anemia (15.2% vs. 21.2%), thrombocytopenia (15.2% vs. 11.5%), and infectious pneumonia (10.6% vs. 1.9%) in BID and QD groups, respectively. By comparing the two groups, the incidence of adverse events (AEs) were similar, except for drug-related serious AEs (24.2% vs. 9.6%) and AEs leading to treatment discontinuation (15.2% vs. 7.7%), which were higher in BID group. The percentages of AEs resulting in death were comparable, with 6.1% in BID and 5.8% in QD group. These analyses further support the long-term durable efficacy and acceptable safety of jaktinib at 100 mg BID and 200 mg QD doses for treating MF.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

Pure red cell aplasia and minimal residual disease conversion associated with immune reconstitution in a patient with high-risk multiple myeloma.

A second bone marrow aspiration and biopsy showed pure red cell aplasia in this case.

Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China.

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0-3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5-7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival.

Patient-Reported Outcomes in Young Adults with Myeloproliferative Neoplasms.

INTRODUCTION: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare. METHODS: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years). RESULTS: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment. CONCLUSIONS: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients.

Front-line treatment efficacy and clinical outcomes of elderly patients with multiple myeloma in a real-world setting: A multicenter retrospective study in China.

BACKGROUND: The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. METHODS: We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens. RESULTS: The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS. CONCLUSION: Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.

Pathophysiology and therapeutic advances in myeloma bone disease.

Bone disease is the most common complication in patients with multiple myeloma (MM), and it may lead to skeletal-related events (SREs) such as bone pain, pathological fractures, and spinal cord compression, which impair a patients' quality of life and survival. The pathogenesis of myeloma bone disease (MBD) involves disruption of bone reconstitution balance including excessive activation of osteoclasts, inhibition of osteoblasts, and participation of osteocytes and bone marrow stromal cells. Various factors, such as the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG), dickkopf-1 (DKK-1), sclerostin, and activin-A, are involved in the development of MBD. Bisphosphonates and the anti-RANKL antibody denosumab are currently the main treatment options for MBD, delaying the onset of SREs. Denosumab is preferred in patients with MM and renal dysfunction. Although effective drugs have been approved, antimyeloma therapy is the most important method for controlling bone disease.

Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naïve patients with myelofibrosis: Results of a phase II trial.

Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.

Efficacy and safety of blinatumomab in Chinese adults with Ph-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia: A multicenter open-label single-arm China registrational study.

OBJECTIVES: The prognosis for adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. Blinatumomab is a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule approved globally for the treatment of BCP-ALL in adults and children. This multicenter open-label single-arm China registrational study evaluated the safety, efficacy, and pharmacokinetics of blinatumomab in Chinese adults with Philadelphia chromosome-negative (Ph-) R/R BCP-ALL (NCT03476239). METHODS: Patients aged ≥ 18 years were treated with up to 5 cycles of blinatumomab. The primary objective was to evaluate the hematological response rate (complete remission/complete remission with partial hematological recovery [CR/CRh]) within 2 cycles of blinatumomab. RESULTS: At the interim analysis (April 12, 2019), 90 patients (median age 31.5 years [range: 18-74]; 53.3% female; 77.8% with bone marrow blasts ≥ 50% at study entry) were enrolled at 23 study centers in China and had received blinatumomab. As of data cutoff, 43 patients (47.8%) continued the study. The CR/CRh rate within 2 cycles of blinatumomab was 45.6% (41/90 [CR, 37; CRh, 4]; 95% CI: 35.0-56.4). Median overall survival was 9.2 months (95% CI: 6.5-11.7); median relapse-free survival was 4.3 months (95% CI: 3.2-9.4). Mean serum concentration at steady-state and systemic clearance of blinatumomab in Chinese patients were within the range reported in adults from global clinical trials. No new safety risks were identified in Chinese patients. CONCLUSIONS: The efficacy and safety of blinatumomab in these heavily pre-treated Chinese patients with Ph- R/R BCP-ALL is comparable to that for patients within global clinical trials.