Dispenzieri, Angela

ABSTRACTThe optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34+ cell dose were collected. Full‐dose melphalan (≥ 180 mg/m2) was administered in 63.7% of the patients, and 80.4% had melphalan split into 2‐day conditioning. A rest day (day −1) between the conditioning regimen and stem cell infusion was provided in 52.5% of patients. The median infused CD34+ cell count was 4.7 × 106/kg. An infused CD34+ cell count ≥ 4.5 × 106/kg was associated with a shorter time to neutrophil and platelet engraftment. In a nominal regression analysis, full‐dose melphalan, 1‐day melphalan conditioning, and omitting a rest day between conditioning and stem cell infusion were independent predictors of post‐ASCT higher deep hematological response. The median follow‐up was 8.6 years, and 38% of patients died. Independent predictors of superior overall survival in multivariate Cox regression analysis included full‐dose melphalan, having no rest day, and infused CD34+ cells ≥ 4.5 × 106/kg. Independent predictors of higher day‐100 transplant‐related mortality (TRM) in nominal logistic regression analysis included poorer performance status, NT‐proBNP/BNP ≥ 1800/400 pg/mL, serum albumin < 2.5 g/dL, CD34+ cells < 4.5 × 106/kg, and not having a rest day. In conclusion, 1 day of melphalan conditioning and administration of CD34+ cells ≥ 4.5 × 106/kg are recommended for ASCT in AL amyloidosis.

Abstract Castleman disease (CD) describes a group of rare lymphoproliferative disorders that exhibit a wide range of symptomatology and degree of lymphadenopathy, particularly across the 2 forms of CD with unknown etiology, unicentric CD (UCD), and human herpesvirus-8–negative/idiopathic multicentric CD (iMCD). Whereas UCD cases typically present with localized lymphadenopathy and mild symptoms, iMCD involves multicentric lymphadenopathy and cytokine storm–driven symptoms with 3 recognized clinical phenotypes. Increasingly, there are anecdotal reports of cases that do not fit into this framework, but these cases have not been systematically described. Herein, we use the ACCELERATE natural history registry to characterize the spectrum of CD based on disease features, symptomatology, and severity. Our results characterize a cohort of 179 CD cases, which were reviewed and confirmed by an expert panel of clinicians and hematopathologists. We show that patients with CD present on a continuous spectrum of clinical phenotypes, and we describe oligocentric CD (OligoCD), an intermediate phenotype that does not fit the criteria for UCD or iMCD. These cases tend to have “oligocentric” lymphadenopathy (median [interquartile range] regions of lymphadenopathy, 3.0 [2.0-4.0]) in a regional pattern and exhibit a mild clinical phenotype that is more similar to UCD than iMCD. We also show that patients with OligoCD are inconsistently categorized as UCD vs iMCD, highlighting the need for this characterization. Future data collected through ACCELERATE may further elucidate the natural history and risk profile of these patients.

Abstract In this study, we first analyzed data from 147 patients with solitary plasmacytomas treated at the Mayo Clinic between 2005 and 2022 and then expanded our investigation through a systematic review and meta-analysis of 62 studies, encompassing 3487 patients from the years 1960 to 2022. Our findings reveal that patients with up to 10% clonal plasma cells in their bone marrow (BM), denoted as plasmacytoma +, had a significantly reduced median disease-free survival (DFS) of 15.7 months vs 79 months, P &lt; .05, observed in patients with true solitary plasmacytomas, with no clonal cells in the BM. Risk factors identified for shorter DFS included the presence of clonal plasma cells in the marrow and a difference between involved and uninvolved free light chains of &gt;5 mg/dL. The meta-analysis portion of our study highlighted a male predominance among patients, with a median age of 58 years, and confirmed radiation therapy as the predominant treatment modality. We also found that DFS rates at 3, 5, and 10 years were 66.9%, 55%, and 42.1%, respectively, and noted a significant difference in outcomes between patients with bone and extramedullary plasmacytomas, with the latter group exhibiting better survival rates. This dual-faceted approach provides a thorough overview of survival rates and critical risk factors for patients with plasmacytoma, underscoring the vital role of accurate disease staging at diagnosis and the impact of tumor location on patient prognosis.

Abstract Several tools have been proposed for assessing frailty in multiple myeloma (MM), but most are based on clinical trial data sets. There are also limited data on the association between frailty and patient-reported outcomes and on the prognostic value of social determinants of health. This study evaluates the prognostic impact of frailty, based on the cumulative deficit frailty index (FI), and relationship and socioeconomic status (SES) in patients with newly diagnosed MM. This retrospective study included 515 patients with MM seen at Mayo Clinic (Rochester, MN) at diagnosis between 2005 and 2018. The FI was calculated using patient-reported data on activities of daily living and comorbidity data, with items scored as 0, 0.5, or 1, in which 1 indicated a deficit. The FI was calculated by dividing the total score by the number of nonmissing items. Frailty was defined as FI ≥0.15; 61% were nonfrail, and 39% were frail. Frailty and nonmarried/relationship status were associated with higher disease stage, decreased the likelihood of early transplantation, and independently associated with decreased survival. SES was not independently associated with survival. Frail patients reported worse scores for fatigue, pain, and quality of life. Approximately a quarter of patients had a deterioration in frailty status at 3 to 12 months, and &lt;10% had improvement. In conclusion, a cumulative deficit FI was associated with higher symptom burden and decreased survival in a real-world cohort of patients with newly diagnosed MM. Frailty status is dynamic and should be reassessed during treatment. Social support has prognostic value and should be evaluated in clinical practice.

Abstract Patient-reported outcomes (PROs) are associated with treatment outcomes in multiple myeloma (MM) in the clinical trial setting. However, most PRO tools are time consuming, which hinders use in routine practice. Our institution incorporated a “Hematology Patient-Reported Symptom Screen” (HPRSS), a 3-item questionnaire for fatigue, pain, and quality of life (QOL). The main objective of this study was to evaluate the impact of these symptoms on progression-free survival (PFS) and overall survival (OS) in a real-world cohort of patients with newly diagnosed MM. This retrospective study included patients with MM diagnosed between April 2011 and December 2017, seen at Mayo Clinic (Rochester, MN), who completed the HPRSS. Patients rated their symptoms on a scale from 0 to 10. Clinically relevant symptoms were defined as scores ≥5 for pain and fatigue, and ≤5 for QOL. At diagnosis, 735 patients had scores for all domains. The median follow-up was 8.1 years. Age was associated with increased odds of fatigue and decreased QOL. Female sex and comorbidities were associated with fatigue and pain. Higher disease stage, anemia, lytic lesions, and increased plasma cell burden were associated with fatigue, pain, and decreased QOL. Clinically relevant fatigue, pain, and decreased QOL were associated with decreased PFS and OS. On multivariate analysis including age, International Staging System III, high-risk cytogenetics, and postinduction transplantation, fatigue and decreased QOL were independently associated with decreased OS. A composite HPRSS score stratified patients into 3 groups with distinct OS. Patient-reported symptoms are prognostic in patients with newly diagnosed MM. The prognostic values of fatigue and decreased QOL are independent of age, disease stage, and transplant status.

Abstract As patients with relapsed/refractory multiple myeloma (RRMM) continue to live longer, they might get exposed to most available drugs and drug classes during the disease course. For such late line RRMM or among patients without access to novel therapies, retreatment with a drug that the disease had previously been refractory to might be one option. In this retrospective study, we describe 315 patients with RRMM at our institution who were retreated with a drug that the disease had been previously refractory to. We found an overall response rate of 56.2% and a median progression-free survival (PFS) of 11 months with retreatment. Patients with a longer time on initial therapy with the index drug (&gt;28.4 months) had a superior PFS with retreatment (median PFS, 16.9 vs 8.1 months; P &lt; .001). Similarly, patients with a longer time gap between the initial line of therapy with index drug and retreatment with index drug (&gt;46.1 months) had better PFS with retreatment (28.2 vs 8.9 months; P = .016). In conclusion, retreatment with a previously refractory drug is a viable therapeutic option for RRMM, with the most significant benefit derived in disease demonstrating sensitivity to initial drug exposure and among those with a longer gap between initial drug exposure and retreatment.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant disorder. The current standard of care is not to screen for MGUS, so it is often incidentally diagnosed in the clinic. It is unknown whether the outcomes of screened vs clinically detected MGUS differ. We compared the progression risk between screened vs clinical MGUS cohorts and assessed whether the MGUS detection method affected risk prediction of established clinical factors (score). We included 379 screened MGUS cases from the Olmsted County population-based study and 1384 patients with MGUS diagnosed during routine clinical evaluation at Mayo Clinic. Median follow-up time for the screened vs clinical cohort was 26.6 and 40.1 years, respectively. Accounting for death as a competing risk, the cumulative incidence of progression at 25 years was similar in the screened (11.1% [95% confidence interval [CI], 8.3-14.8]) vs clinical (10.1% [95% CI, 8.6-11.8]) MGUS cohorts, even when stratified by sex, age, or the baseline MGUS risk score. Overall, 0.9 (95% CI, 0.6-1.2) of patients with screened MGUS vs 1.0 (95% CI, 0.9-1.2) of those with clinically detected MGUS experienced disease progression for every 100 person-years of follow-up. MGUS detection method did not modify the association between MGUS risk score and progression risk (pinteraction = 0.217) and did not add to known risk factors for progression (likelihood ratio test; P = .839). Here, we show that progression risk among patients with screened vs clinically detected heavy-chain MGUS was similar. Future studies are needed to assess whether tailored follow-up of patients with screened MGUS affects clinical outcomes.