Warsame, Rahma

AbstractDetection of myeloma progression (PD) relies on serial 24‐h urinary M protein measurements in patients without measurable serum M spike. We examined whether serial difference free light chain (dFLC) levels could be used as a surrogate for serial 24‐h urine M protein measurements in monitoring for PD in patients with baseline measurable urine M protein. We studied 122 patients who had serial measurement of urine M protein and serum FLC and had demonstrated PD. The median increase in dFLC with progression as defined by urine M spike was 110% (IQR: 55‐312) and median absolute increase was 74 mg/dL; while 89% of patients had dFLC increase ≥ 25%, 94% had absolute increase in dFLC > 10 mg/dL, and 98% met at least 1 of these 2 criteria at PD. In patients with baseline measurable serum FLC (n = 118), 89% had increase in dFLC ≥ 25%, 97% had dFLC increase of > 10 mg/dL, and 98% had 1 of the 2. We conclude that serial dFLC assessments can be used in place of serial 24‐h urine protein assessments during myeloma surveillance to monitor for PD. Once patients have an absolute increase in dFLC of >10 mg/dL from the nadir, a 24‐h urine collection can then be assessed to document PD as per the International Myeloma Working Group criteria.

SummaryThe optimal duration of induction therapy (IT) in transplant‐eligible multiple myeloma (MM) patients in not well defined, resulting in a wide variation in clinical practice. The objective of our study was to determine whether the duration of IT in patients undergoing upfront autologous stem cell transplantation (ASCT) has an impact on progression‐free survival (PFS) in the era of proteasome inhibitors and immunomodulatory drugs. A total of 596 patients who underwent ASCT at Mayo Clinic between 2007 and 2014 were included. The patients were divided into two cohorts based on the duration of IT: IT ≤ 4 and IT > 4 months. At a median follow‐up of 54·5 months from ASCT, the median PFS in the IT ≤ 4 group was 28 months [95% confidence interval (CI), 25–33], compared to 26 months in the IT > 4 group (95% CI, 24–31) [P = 0·605]. There was no significant difference in overall survival (OS) in the two groups (P = 0·904). The lack of impact of IT duration on PFS and OS was consistent in subgroups with high‐risk features at diagnosis (International Staging System III or high‐risk cytogenetics) and different depths of pre‐transplant response [≥very good partial response (VGPR) and <VGPR]. In conclusion, prolonging the duration of IT beyond 4 months does not impact survival in patients with newly diagnosed MM who complete a single line of IT followed by consolidation with ASCT.

AbstractResponse rates in newly diagnosed multiple myeloma have improved dramatically with the introduction of highly effective novel therapies. However, survival in patients achieving optimal responses to initial treatment can vary significantly, and new prognostic indicators are required to improve risk stratification. We investigated the relationship between time to plateau (TPlat) and survival in 1099 newly diagnosed patients treated with novel agents at our institution from 2005 to 2015.TPlatwas defined as time from initiation of first‐line therapy to best response to first‐line therapy. The medianTPlatwas 4.9 months (0.7‐58.6) and plateau duration was 1.8 years (0.2‐11.0). Patients who required > 120 days to achieve a plateau had longer modified overall survival (mOS) and progression free survival (mPFS) calculated from a landmark of best response (P < .001 for both comparisons). Statistically significant improvement in mOS was retained in subgroup analysis based on age and whether patients received upfront autologous hematopoietic stem cell transplantation (ASCT) (P < .001 for all comparisons). Our results suggest that patients who respond more gradually to initial therapy (TPlat > 120 days) experience longer survival compared to more rapid responders. Patients with a prolongedTPlatcould represent an “ongoing responder” phenotype that portends a survival advantage independent of treatment with upfront ASCT, depth of response, and biologic markers such as ISS stage and cytogenetic risk.

Key Points λ Light chain AL amyloidosis is associated with a shorter PFS and OS compared with κ. Light chain type predicts likelihood of organ involvement in AL amyloidosis.

Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.

This commentary takes a look back at views on complementary and alternative medicine and reflects on how those views have evolved, advocating for a conversation around complementary and alternative medicine in cancer care that is more nuanced, patient-centered, and respectful to best meet the needs of patients in the coming decades.

32 Background: The link between patient concerns and clinical systems delivery is often suboptimal. We developed a case management system for palliative care which transforms the patient’s greatest concerns into actionable clinical pathways. Methods: The system collects patients’ single greatest and second greatest concern plus Quality of Life (QOL) data (pain, fatigue and overall QOL single-items scored 0-10 with 10 representing worst pain/fatigue, or best QOL) and produces a report to guide the physician and patient. The system presents ten “buttons” in a xylophone-like grid: Personal Relationships, Monitoring Health, Emotional Health, Money, Health Behaviors, Medication Troubles, Care Access, Work Worries, Physical Health and Care Planning. We performed a quality improvement study at Mayo Clinic sites. Results: 409 patients participated in at least one survey from 11/04/2015 to 9/22/2016 (620 total surveys). The most common Main Concern was Physical Health 265/620 (43%) followed by Monitoring Health (17%), Medication (8%), and Emotional Health, Money, and Health Behaviors (7% each), Personal Relationships (6%). Future Care Planning, Work, and Care Access/Coordination were rarely chosen ( < 5%). The most common Second greatest concern was Health Behaviors 73/409 (18%) followed by Physical Health (17%). 93/122 (67%) patients changed their greatest concern from baseline to subsequent visits. The mean QOL, fatigue and pain at baseline were 4.8, 6.0 and 4.8 respectively, indicating substantial clinically significant deficits. Post baseline mean scores improved by a maximum of 0.8, 1.1, and 0.9 points respectively, representing clinically meaningful effects. On average it took 8 minutes for patients to use the system. Conclusions: The system was quick and easy to utilize. The personal impact concerns (physical/emotional health, medications) were most often cited as the greatest concern, while care issues were de-emphasized by patients. Patients and physicians praised the system for making visits more efficient and raising issues that otherwise might not have been addressed. This system has the potential to improve patient well-being and clinical outcomes, as well as to reduce burden on clinicians and optimize case management activities.

AbstractExperience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE‐like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent‐to‐treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02‐11.4) separated diagnosis of myeloma and inititation of VPLR. High‐risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1‐14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety‐five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1‐9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression‐free survival was 3.1 months (95% CI, 1.9‐3.9) and median overall survival (OS) was 8.1 months (CI, 6.2‐9.9). One‐hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3‐20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4‐3.7]; P = 0.0008) and R‐ISS III stage (HR‐ 2.4 [CI, 1.3‐4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre‐treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.