BackgroundWe intended to investigate the long-term clinical characteristics, responses to therapy and survival in patients with lightchain multiple myeloma (MM).MethodsNinety-six patients were enrolled into the study. There were 42 κ-chain MM patients and 54 λ-chain MM patients. All the patients werestage III in the Durie-Salmonstaging system. Among them, 66 patients received Velcade (bortezomib) treatment and the other 30 did not.ResultsThe main symptoms of these patients included bone pain (77.1%), weakness and fatigue (12.5%), foamy urine (8.3%) and extramedullaryplasmocytomas (33.3%). The overall response rate (ORR) was 95.5% in patients treated with Velcade and 60%in the patients without. The median survival times were 23 months in patients treated with Velcade and 12 months in patients without. The median time of progression-free survival (PFS) was nine months in patients treated with Velcade and five months in patients without. The one-year PFS and two-year PFS were 37% and 25%, 27% and 9% for patients treated with Velcade, or without, respectively. The three-year overall survival (OS) and five-year OS were 33% and 24%, 28% and 9% for patients treated with Velcade, or without, respectively. There was no significance in OS between the two groups (P = 0.335). But there was significant difference in PFS between the two groups (P = 0.036).ConclusionsOur long-term study demonstrated that patients with lightchain myeloma appeared to have more aggressive disease courses and poor outcomes, which could be improved by treatment with Velcade.

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain (AL) amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac AL amyloidosis. Methods: This was a multicenter, open-label randomized controlled trial. Patients with Mayo 2004 stage II-III AL amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression or organ progression (heart, kidney or liver). Hematologic progression was defined based on substantial increase in free light chain. Increase in either N-terminal pro B-type natriuretic peptide or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated using a Cox regression model. Results: 140 patients underwent randomization, with 70 in each group. The median age was 61 (range, 33-78) years with a male: female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32/70 (45.7%) of patients in the doxycycline group and 30/70 (42.9%) of patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio 0.97, 95% CI, 0.59-1.60, p =0.91). Cardiac progression occurred in 29/70 (41.4%) of patients in the doxycycline group and 26/70 (37.1%) of patients in the control group. The death rates for both groups by the end of follow-up was the same, 25/70 (35.7%). There were no significant differences observed for either cardiac PFS (hazard ratio 0.91, 95% CI, 0.54-1.55, p =0.74) or overall survival (hazard ratio 1.04, 95% CI, 0.60-1.81, p =0.89). Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac AL amyloidosis. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03401372.

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n 5 11), 8 mg/kg (n 5 17), and 10 mg/kg (n 5 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial.