Early autologous hematopoietic cell transplantation (AHCT) with post‐transplant maintenance therapy is standard of care in multiple myeloma (MM). While short‐term quality of life (QOL) deterioration ...after AHCT is known, the long‐term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT‐BMT scores up to 4 years post‐AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as ‘none/mild’ for scores 0–2 and ‘moderate/severe’ for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1‐year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow‐up was 6 years (range, 0.4–8.5 years). FACT‐BMT scores improved between enrollment and 1‐year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1‐year, and 32% at 4 years post‐AHCT. Predictors of low symptom burden at 1‐year included low symptom burden at baseline: OR 2.7 (1.8–4.1), p < 0.0001; older age: OR 2.1 (1.3–3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4–3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT‐BMT and subscale scores to population norms by 1‐year post‐transplant, though many patients continue to report moderate to severe severity in some symptoms at 1‐year and beyond.
Change in FACT‐BMT score between baseline and 1‐year post‐transplant after AHCT. Q4 represents the highest QOL score quartile and Q1 represents the lowest QOL score quartile.
Background
Lenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression‐free survival and overall survival. However, patients with ...high‐risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard‐risk patients. The authors sought to determine the outcomes of bortezomib‐based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT.
Methods
In total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet novel‐agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain.
Results
Three hundred fifty‐seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib‐based maintenance (with bortezomib alone in 58%). Patients in the bortezomib‐based maintenance group were more likely to harbor two or more high‐risk abnormalities and International Staging System stage III disease (30% vs. 22%; p = .01) compared with the lenalidomide group (24% vs. 15%; p < .01). Patients who were receiving lenalidomide maintenance had superior progression‐free survival at 2 years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p = .009). Overall survival at 2 years was also superior in the lenalidomide group (93% vs. 84%; p = .001).
Conclusions
No superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post‐transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.
No clear benefit was observed for nonlenalidomide maintenance strategies in patients with high‐risk multiple myeloma. Novel therapeutic strategies are needed for post‐transplant maintenance in this setting.
Abstract
An insulator-to-metal transition (IMT) is an emergent characteristic of quantum materials. When the IMT occurs in materials with interacting electronic and lattice degrees of freedom, it is ...often difficult to determine if the energy gap in the insulating state is formed by Mott electron–electron correlation or by Peierls charge-density wave (CDW) ordering. To solve this problem, we investigate a representative material, vanadium dioxide (VO
2
), which exhibits both strong electron–electron interaction and CDW ordering. For this research, VO
2
films of different thicknesses on rutile (001) TiO
2
substrates have been fabricated. X-ray diffraction (XRD) data show that ultrathin VO
2
films with thickness below 7.5 nm undergo the IMT between rutile insulator below
T
c
and rutile metal above
T
c
, while an ultrathin VO
2
film with a thickness of 8 nm experiences the structural phase transition from the monoclinic structure below
T
c
to the rutile structure above
T
c
. Infrared and optical measurements on a film of 7.2 nm thickness, below
T
c
, reveal the energy gap of 0.6 eV in the rutile insulator phase and the absence of the 2.5 eV bonding-antibonding CDW structure. Above
T
c
, a Drude feature in the optical conductivity reveals the IMT to a metallic phase. These results suggest that for VO
2
films below a critical thickness of about 7.5 nm, the IMT occurs in the rutile structure of VO
2
without the Peierls lattice distortion.
In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received ...topotecan 3.5 mg/m(2) intravenously on days -6 to -2, melphalan 70 mg/m(2) intravenously on days -3 and -2 and CY 1 g/m(2) intravenously on days -6, -5 and -4. Overall response rate (ORR) consisting of complete response and partial response (CR+PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45-72) were enrolled. Forty-one patients were treated for consolidation of first remission, while 19 patients had relapsed/refractory disease. ORR was 85% (CR 12%, very good PR 43% and PR 30%). Median time to neutrophil (ANC>0.5 × 10(9)/L) and plt engraftment (>20 × 10(9)/L) was 10 (range 7-12 days) and 9 days (range 6-79 days), respectively. A majority of the common adverse events were grade 1-3 mucositis/stomatitis (65%), grade 1 or 2 nausea (59%) and grade 1 or 2 diarrhea (41%). Median PFS was 18.5 months and median OS has yet not been reached. In conclusion, topotecan, melphalan and CY is a safe and active conditioning regimen for auto hematopoietic SCT in MM. The ORR and PFS were comparable to high-dose melphalan.
We successfully grow corundum structured Ti2O3 films on c-plane sapphire substrates using pulsed laser deposition. Temperature dependent resistivity measurements show that a metal to insulator ...transition (MIT) is suppressed, showing conducting behavior at all temperatures. Samples still show an increase in resistivity as temperature is decreased, a characteristic indicative of a semiconducting phase. Our films exhibit grain size on the order of 30 nm which induce a strain consistent with nanoparticle Ti2O3 showing a (c/a) ratio of 2.7. The imposed strain causes an increase in the c-axis length as the temperature is decreased, and thereby suppresses the transition to an insulating phase. Our optical data agrees with this result, showing the lack of a band gap and the electronic structure consistent with bulk high temperature metallic Ti2O3 with the a1g - egπ interband transition shifted down to 0.7 eV from its bulk insulating value of ∼1 eV.
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•Deposited corundum structured Ti2O3 films on c-cut sapphire substrates.•Metal-insulator transition of Ti2O3 films is suppressed by film strain.•Imposed film strain prevents the band gap from opening in Ti2O3 film.•New electrical and optical properties of Ti2O3 films compared to bulk form.
Background
The prognostic significance of minimal residual disease (MRD) status before autologous hematopoietic stem cell transplantation (autoHCT) in patients with multiple myeloma (MM) has not been ...clearly elucidated.
Methods
Retrospective single‐center study of adult MM patients who achieved ≥very good partial response (VGPR) after induction therapy from 2015 to 2021 received upfront autoHCT and had available pretransplant MRD status by next‐generation flow cytometry. The cohort was divided into pretransplant MRD‐negative (MRDneg) and MRD‐positive (MRDpos) groups.
Results
A total of 733 patients were included in our analysis; 425 were MRDneg and 308 MRDpos at autoHCT. In the MRDpos group, more patients had high‐risk cytogenetic abnormalities (48% vs. 38%, respectively; p = .025), whereas fewer patients achieved ≥CR before autoHCT (14% vs. 40%; p < .001). At day 100 after autoHCT, 37% of the MRDpos versus 71% of the MRDneg achieved ≥CR, and at best posttransplant response 65% versus 88% achieved ≥CR, respectively. After a median follow‐up of 27.6 months (range, 0.7–82.3), the median PFS was significantly shorter for patients in the MRDpos group compared to the MRDneg group: 48.2 months (95% confidence interval CI, 0.3–80.5) versus 80.1 months (95% CI, 0.5–80.1), respectively (p < .001). There was no significant difference in overall survival between the two groups (p = .41). Pretransplant MRDpos status was predictive of shorter PFS in multivariate analysis (hazard ratio, 1.80; 95% CI, 1.31–2.46; p < .001). The impact of pretransplant MRD status was retained in most of the examined subgroups.
Conclusions
In patients achieving ≥VGPR to induction, pretransplant MRDpos status was associated with a lower CR rate after autoHCT and a shorter PFS.
This retrospective single‐center study evaluated the prognostic impact of pretransplant minimal residual disease (MRD) status by next‐generation flow cytometry in 733 multiple myeloma patients who achieved ≥ very good partial response after induction therapy and received upfront autologous hematopoietic stem cell transplantation (autoHCT). Pretransplant MRD positivity was associated with a lower complete remission rate after autoHCT and a shorter progression‐free survival.
Summary
The second revision of the International Staging System (R2‐ISS) is a simple tool to risk‐stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective ...analysis to evaluate the utility of R2‐ISS in NDMM patients who underwent up‐front autologous haematopoietic stem cell transplantation (auto‐HCT). A total of 1291 patients were included, with a median age of 62 years (range 29–83). The distribution of R2‐ISS stages was: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III and 131 (10%) stage IV. With a median follow‐up of 42.2 months (range 0.3–181.0), the median PFS was 73.0, 65.2, 44.0 and 24.8 months, (p < 0.001) and the median OS was 130.8, 128.5, 94.2 and 61.4 months (p < 0.001) for patients with R2‐ISS stages I, II, III and IV respectively. On multivariable analysis (MVA) for PFS, using R2‐ISS stage I as reference, R2‐ISS stages III (hazard ratio 95% confidence interval, 1.55 1.05–2.29; p = 0.028) and IV (2.04 1.24–3.36; p = 0.005) were associated with significantly inferior PFS. In the MVA of OS, using R2‐ISS stage I as reference, only R2‐ISS stage IV was associated with significantly inferior OS (2.43 1.18–5.01; p = 0.017). Overall, we found that R2‐ISS is a reliable prognostic tool for NDMM patients undergoing up‐front auto‐HCT.
The second revision of the International Staging System (R2‐ISS) is a simple tool to risk‐stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective analysis to evaluate the utility of R2‐ISS in NDMM patients who underwent up‐front autologous haematopoietic stem cell transplantation (auto‐HCT). A total of 1291 patients were included in this analysis. The median progression‐free survival was 73.0, 65.2, 44.0 and 24.8 months, (p < 0.001) and the median overall survival was 130.8, 128.5, 94.2 and 61.4 months (p < 0.001) for patients with R2‐ISS stages I, II, III and IV disease respectively. Overall, we found that R2‐ISS is a reliable prognostic tool for NDMM patients undergoing up‐front auto‐HCT.
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