Hobbs, Miriam

AbstractAchievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Key Points Organ progression at second-line therapy predicated inferior survival. Patients relapsing from >VGPR had a longer time to develop organ progression.

AbstractOutside of clinical trials, experience with daratumumab‐based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43‐93) years. High‐risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1‐14) and time to first DCT from diagnosis was 4.3 years (range, 0.4‐13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty‐two (41%), 34 (27%), 23 (18%), and 17 (14%) received DPd, DRd, DVd and “other” DCTs, respectively. Overall response rate was 47%. Median follow‐up was 5.5 months (95% CI, 4.2‐6.1). Median progression‐free survival (PFS) was 5.5 months (95% CI, 4.2‐7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta‐refractory MM (n = 8) vs quadruple refractory MM (n = 18) and others (n = 100) (2.2 [95% CI, 1‐2.4] vs 3.1 [95% CI, 2.1‐NR] vs 5.9 [95% CI, 5.0‐NR]; P < .001); those who were refractory to ≥1 agents used in the DCT vs others (4.9 [95% CI, 3.1‐6.0] vs 8.2 [95% CI, 4.6‐NR]; P = .02); and those who received >2 prior therapies vs others (5.0 months [95% CI, 3.7‐5.9] vs NR [95% CI, NR‐NR]; P = .002). Non‐hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pretreated patients are lower than those reported in clinical trials.

Abstract We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS—39, myeloma—20, lymphoplasmacytic lymphoma—21 and others—14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia‐related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one‐half.

AbstractWe analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1‐93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.

Key Points Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade. Six-month mortality among transplant ineligible patients has declined since 2005.