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Induction therapy for multiple myeloma is traditionally capped at 6 cycles of lenalidomide due to concerns that longer treatment compromises the ability to collect sufficient stem cells for autologous stem cell transplantation (ASCT). However, during the COVID-19 pandemic, many of our patients received prolonged lenalidomide induction due to concerns about proceeding to ASCT. We investigated whether prolonged induction with lenalidomide affects the efficacy of stem cell collection among patients mobilized with cyclophosphamide and/or plerixafor.This single center, retrospective study included patients who were treated with lenalidomide induction regimens, received mobilization with cyclophosphamide or plerixafor, and underwent apheresis in preparation for ASCT. 94 patients were included, 40 of whom received prolonged induction with6 cycles of lenalidomide containing regimen.Patients who received prolonged induction were more likely to require1 day of apheresis (38% vs. 15%; OR 3.45; P = .0154), and there was a significant correlation between the duration of lenalidomide treatment and the apheresis time required to collect sufficient cells for transplant (RAmong patients treated with6 cycles of lenalidomide, mobilization augmented with cyclophosphamide and/or plerixafor will likely facilitate sufficient stem cell harvest to permit ASCT.

Background CC-220-MM-001 (NCT02773030) is an ongoing phase 1/2 study evaluating the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, and preliminary efficacy of IBER, an oral, novel cereblon E3 ligase modulator (CELMoD®) compound, with different treatment combinations in independent cohorts, in pts with MM. Here we report results from the IBER+DARA+DEX (IberDd), IBER+BORT+DEX (IberVd), and IBER+CFZ+DEX (IberKd) cohorts in RRMM. Methods Eligible pts received ≥2 (IberDd and IberKd cohorts) or ≥1 prior regimens (IberVd cohort), containing lenalidomide or pomalidomide, and a proteasome inhibitor. All pts had progressed ≤60 days from last therapy. Escalating oral doses of IBER were given on day (D)1–21 of each 28-D cycle in the IberDd cohort and in the IberKd cohort with weekly CFZ, and on D1–14 of each 21-D cycle in the IberVd cohort. DEX was given weekly in all 3 cohorts. Results As of April 8, 2021, 43 pts had received IberDd, 25 IberVd, and 9 IberKd. Median age was 67, 64, and 61 years, and median time since diagnosis was 7.35, 7.1, and 6.7 years in the IberDd, IberVd, and IberKd cohorts, respectively. Extramedullary plasmacytomas were present in 7 (16%), 4 (16%), and 2 (22%) pts in the IberDd, IberVd, and IberKd cohorts, respectively. Exposure to prior regimens was heterogeneous; all pts were refractory to their last prior regimen and ≥33% pts in the 3 cohorts were triple-class refractory. IBER doses ranged from 1.0 to 1.6 mg. Median follow-up was 4.17, 4.86, and 5.03 months, 22 (51%), 6 (24%), and 5 (56%) pts continue on treatment, and median cycles received were 4, 6, and 5 with IberDd, IberVd, and IberKd, respectively. Hematologic grade (G) 3–4 treatment-emergent adverse events (TEAEs) of interest included neutropenia (67%), leukopenia (23%), anemia (21%), and febrile neutropenia (5%) with IberDd; neutropenia (28%) and thrombocytopenia (24%) with IberVd; and lymphopenia (44%) and neutropenia (33%) with IberKd. Neutropenia was manageable with G-CSF. Occurrence of non-hematologic TEAEs was low, with very few G3–4 fatigue, rash, and gastrointestinal disorders. The overall response rate was 46% with IberDd, 56% with IberVd, and 50% with IberKd, including a VGPR or better of 24%, 28%, and 38%, respectively. Median time to response was 4.1 (4.0–12.0), 3.6 (3.0–13.1), and 4.1 (4.1–8.1) weeks, in the IberDd, IberVd, and IberKd cohorts, respectively. Median duration of response is 35.7 weeks in the IberVd cohort (not reached in the other cohorts). RP2D was determined at 1.6 mg in the IberDd cohort; dose evaluation continues in the other cohorts. Conclusions In pts with heavily pretreated RRMM, IberDd, IberVd, and IberKd showed a tolerable safety profile and promising efficacy. These results support further development of IBER-based regimens in MM, including the initiation of phase 3 combination studies. Previously published in Lonial S, et al. HemaSphere 2021;5(S2):49.

Context: To optimize treatment of Black pts with multiple myeloma, a greater understanding of differences in outcomes in Black pts vs. White pts is needed. In GRIFFIN, DARA plus RVd (D-RVd) improved rates and depth of response in autologous stem cell transplant (ASCT)-eligible NDMM pts. Here, we report a subgroup analysis of Black pts from GRIFFIN. Design: Between 2016 and 2018, pts in the United States were randomized 1:1 to RVd ± DARA and received 4 induction cycles, high-dose therapy, ASCT, 2 consolidation cycles, and maintenance with R ± DARA for 24 mo. The pre-specified primary endpoint was stringent complete response (sCR) rate by end of consolidation, which occurred at a median follow-up of 13.5 mo. Results below are based on longer follow-up (22.1 mo). Results: Two hundred seven pts (D-RVd, n=104; RVd, n=103) were randomized; 32 (15%) pts were Black (D-RVd, n=14; RVd, n=18), and 161 (78%) pts were White (D-RVd, n=85; RVd, n=76). Baseline demographics were generally similar between treatment arms in Black and White pts. D-RVd vs RVd improved the sCR rate by end of consolidation in Black (10 [71%]; 6 [33%]) and White pts (35 [43%]; 24 [34%]). Including post-consolidation data, sCR with D-RVd vs. RVd was achieved by 12 (86%) and 7 (39%) Black pts and 50 (61%) and 33 (46%) White pts. ORR by end of consolidation was improved for D-RVd vs. RVd in Black pts (14 [100%] vs. 17 [94%]), as were rates of ≥CR (12 [86%] vs. 7 [39%]) and minimal residual disease at 10−5 (5 [36%] vs. 3 [17%]). Grade 3/4 TEAEs (≥25%) with D-RVd/RVd included neutropenia (Black pts, 50%/22%; White pts, 41%/16%), lymphopenia (29%/39%; 23%/16%), and thrombocytopenia (29%/11%; 14%/8%). Grade 3/4 infections for D-RVd/RVd occurred in 36%/17% of Black and 20%/23% of White pts. IRRs occurred in 29% of Black and 45% of White pts. Conclusions: GRIFFIN demonstrated that D-RVd improved responses in the Black NDMM pt subgroup, but larger studies are needed to better define the magnitude of DARA benefit in Black pts. Improved recruitment of Black pts in clinical trials is needed to understand disease biology and response to therapy among racial groups.

This paper presents a procedure to assess the mobilized pile side and tip resistance versus pile head and tip settlement under axial load in clay soil. The load transfer (t–z) curve is evaluated at any point on the loaded pile based on the combined pile tip/side resistance–displacement mechanisms along the length of the pile. Unlike current methods that assume the pile settlements as a percentage of the pile/shaft diameter, the presented technique determines the side and tip resistance of the pile and the associated pile settlement under existing load based on the current stress/strain level in the surrounding soil up to failure (excessive settlement). The technique employs the concepts of the elastic theory and Ramberg–Osgood characterization of the stress–strain behavior of the clay soil. Case studies are also presented to exhibit the capabilities of the proposed procedure. The good agreement between measured and calculated load transfer curves along the pile and pile tip resistance versus pile head, side, and tip displacements shows the consistency of the proposed procedure. A computer code is developed to employ the presented technique.

With a capacity of 86 MCM, King Talal Reservoir is considered a major water supply in Jordan. It was built exclusively to irrigate the land in the Jordan Valley. Unexpectedly, the design capacity of the reservoir was confronted by the elevated sediment inflows during and after the construction of the Irbid–Amman Highway in 1987. Since then the annual sediment inflow measured at the mouth of the reservoir was higher than expected in a similar year. Notably, the over-wet season of 1991/2, as a result of six major landslides along the highway, registered the highest sediment inflow into the reservoir. In the present work the fractional contribution of these landslides to total sediment yield at the reservoir was evaluated. The evaluation was made by applying the well-known erosion model, AGNPS (Young et al., USDA Conservation Research Report 35, 1987). To calibrate the model, it was successively applied from 1980/1 to 1990/1 on the measured sediment data before the occurrence of landslides. With a slight tune-up of some of the King Talal watershed erosion variables, fairly good agreement was obtained in some years. However, the disagreement noticed in other years might be attributed to some conservation measures practised in the watershed. Because the serious landslides occurred in the wet season of 1991/2, the model was run for the two scenarios in this year: with and without landslides. The difference in results represents the contribution of landslides to sediment yield at the reservoir. It is concluded, based on these results, that landslides, if continued without control, will definitely jeopardize the design capacity of the reservoir.

The oxidative methylation of acetonitrile with methane to acrylonitrile occurs more actively and selectively over bialkali promoted CaO catalysts than over any monoalkali promoted system. The most effective catalytic systems are obtained with Li A + Cs A , Na A + Cs A , or K A + Cs A (A = SO 2− 4 , OH − , C1 − , CH 3 COO − , CO 2− 3 , or NO − 3 ) supported on CaO, containing total alkali loadings of 10 mol% with equal molar amounts of both alkalis. At 750°C, under atmospheric pressure, at CH 4 : O 2 : CH 3 CN : He partial pressure ratios of 5.0 : 1.0 : 1.5 : 6.5, and at a space velocity of 15,000 cm 3 g −1 V −1 , the highest selectivity to acrylonitrile (70.0 mol%) and yield (25%) are obtained over (5 mol% Na + + 5 mol% Cs + )/ CaO (prepared from the sulfate precursors). Any bialkali-promoted system containing Rb was less effective, whereas the Li-containing systems, though active initially, gradually lost the activity due to its volatility. The performances of the effective bialkali systems, after an initial increase, remained almost unchanged for a period of 60 h. In contrast, the stability of any monoalkali promoted system with time-on-stream was very low and the maximum initial yield of acrylonitrile was only 11.5% under the aforementioned conditions. The synergistic increase in the catalytic performance of the bialkali promoted CaO is reflected in the synergistic increase of the surface basicity (leading to superbasicity) caused by the high enrichment of the surface layer with the alkali ions. The relationship between the catalytic performances and the physicochemical characteristics of the catalysts revealed by XPS, AAS, and basicity measurements is explored.

The oxidative methylation of toluene with methane to ethylbenzene and styrene has been investigated over various monoalkali-metal-compounds-promoted MgO catalysts and superbasic catalysts prepared by promoting MgO with various binary alkali metal compounds. The experiments have been carried out under atmospheric pressure, at 650-850°C, at a CH4 :O2 : C7H8 : He partial pressure ratio of 14.7 : 2.9 : 1 : 11.8 and at a space velocity of 15,000 cm3 g−1 h−1. The performances of the bialkali-metal-compounds-promoted MgO are much higher than any monoalkali-promoted MgO and are found to strongly depend on the nature of the alkali metal compounds forming the pair, the concentration of the alkali metal ions, and the reaction conditions. The most effective catalytic systems are obtained with MgO promoted with the bialkali metal compounds of LiA + NaA, LiA + CsA, KA + CsA or NaA + CsA (A = SO2−4, OH−, Cl−, CH3COO−, CO2−3 or NO−3) containing total alkali loadings of 10 mol% with equal molar amounts of both alkalis. Any bialkali-promoted system containing rubidium was less effective than those systems. The highest C8-selectivity (57 mol%) and C8-yield (24.2%) with a styrene/ethylbenzene molar ratio of 1.6 were obtained over (5 mol% Na+ + 5 mol% Cs+)/MgO (prepared from the sulfate precursors) at 750°C under the aforementioned conditions. The total C8-selectivity and the total C8-yield over the bialkali-promoted systems remained almost unchanged for a period of 60 h. In contrast, the maximum C8-yield over any monoalkali-promoted system never exceeded 11.6% (styrene/ethylbenzene = 1.4) under the same conditions and the stability with time-on-stream was less prominent. The relationship between the catalytic performances and the physicochemical characteristics of the catalysts revealed by XPS and basicity measurements is explored. The relatively high performances of the bialkali-metal-compounds-promoted MgO are likely to be related to the synergistic increase in the surface basicity (superbasicity) caused by the enrichment of the surface layer with the alkali ions (Na+ and Cs+).

The selectivity to styrene and ethylbenzene (C8 selectivity), their yields (C8 yield), and the stability with time-on-stream in the oxidative methylation of toluene with methane have been compared for superbasic catalysts prepared by promoting MgO, CaO, SrO or BaO with binary alkali metal compounds. The bi-alkali-promoted substrates are more effective than the mono-alkali promoted systems. The most effective catalytic system (5 mol-% Na+ + 5 mol-% Cs+)/CaO gave a toluene conversion as high as 45.0 mol-% and a total C8 selectivity of 60.0 mol-% (styrene/ethylbenzene = 2.2) resulting in a total C8 yield of 27%, and operated in a stable manner for 60 h. These are the highest values ever reported in the open literature. The bi-alkali-promoted MgO also showed similar performances but somewhat smaller than those of promoted CaO. In contrast, the bi-alkali-promoted SrO and BaO were less effective under the same conditions, both exhibiting much lower performances than the promoted CaO or MgO. In terms of the toluene conversion, the C8 selectivity and the stability with time-on-stream, the following sequence was observed for the bi-alkali-promoted substrates: CaO > MgO > BaO > SrO. The relatively high performances of the bi-alkali-promoted CaO or MgO compared to the mono-alkali ones are attributed to the synergistic increase in surface basicity (superbasicity) caused by the enrichment of the surface with the bi-alkali mixtures. Unlike SrO and BaO, which form stable carbonates with the CO2 formed during the reaction which inhibits the surface basicity, the Ca or Mg carbonates decompose to oxides under the reaction conditions, thereby ensuring a higher catalytic performance. It is shown that there exists an optimum substrate, CaO, which upon promotion with bi-alkali becomes the most effective in the oxidative methylation of toluene.

Upon promoting ZrO2 with alkali metal compounds (chlorides, nitrates, carbonates, or acetates), effective catalytic systems are obtained which are more active, selective, and stable with time-onstream than unpromoted ZrO2 or unsupported promoter compounds at 750°C, PCH4 = 243.2 Torr, CH4/O2 = 4, and a space velocity of 7500 cm3 g−1 h−1. The performance of the catalysts is found to strongly depend on the nature of the alkali salt, the promoter content, the method of catalyst preparation, and the reaction conditions (temperature, partial pressures. CH4/O2 ratio, and contact time). The most effective catalytic system is obtained with Na+-ZrO2-Cl− prepared via the sol-gel method, which leads to a methane conversion of 13.8 mol%, total C2 selectivity of 77 mol% (C2 yield 10.6%), and an ethylene-to-ethane ratio of 3.3 for at least 30 h under the aforementioned conditions and atmospheric pressure. Addition of carbon tetrachloride as a source of chlorine species to the feedstream improves the performance of the catalyst and its stability with time-on-stream. In the latter case, a CH4 conversion of 22.0% and a C2 yield of 17.5% with a C2H4/C2H6 molar ratio of 2.7 are obtained at a space velocity of 3750 cm3 g−1 h−1. In contrast, Na+-ZrO2-Cl− prepared via impregnation, gel-precipitation, physical mixing, or ion-exchange, and the Li-, K-, Rb-, or CsCl-promoted ZrO2 catalysts prepared by any of the above methods, were less effective, even upon the addition of carbon tetrachloride to the feedstream. The relatively high performance of Na+-ZrO2-Cl− (sol-gel) is attributed to the incorporation of Na+Cl− into the ZrO2 matrix, the exposure of an appreciable amount of Na+ and Cl− on the surface, and the increase in basicity and base strength. The relationship between the catalytic performance and the physico-chemical characteristics of the catalysts revealed by XRD, XPS, and basicity (stepwise thermal desorption of CO2) measurements is explored.

Promoting ZrO 2 with Na + Cl − via a sol-gel process, an effective catalytic system is obtained which is more active, selective and stable with time-on-stream than unpromoted ZrO 2 , or any other alkali chloride promoted ZrO 2 in the oxidative coupling of methane at 750°C, atmospheric pressure, CH 4 /O 2 = 4 and a space velocity of 7500 cm 3 g −1 h −1 . Operating at a low partial pressure of the reactants (CH 4 +O 2 = 91.2 Torr, 1 Torr = 133.3 Pa) and the aforementioned conditions, a C 2 yield of 14.1% is obtained. The performance of the alkali metal chloride promoted ZrO 2 is found to depend strongly on the nature of the cation, the method of catalyst preparation, the promoter content and the reaction conditions (temperature, partial pressure, CH 4 /O 2 ratio and space velocity). The relationship between the catalytic performance and the physico-chemical properties of Na + -ZrO 2 -Cl − revealed by X-ray diffraction and X-ray photoelectron spectroscopy is explored.

The magnesia-supported bismuth oxychloride with lithium carbonate present is significantly more effective and stable with time-on-stream than the unsupported or supported systems free of Li 2 CO 3 in the oxidative coupling of methane at 750°C, P CH4 = 20.2 kPa, CH 4 /O 2 = 4, and aspace velocity of 15,000 cm 3 g −1 h −1 . The most effective catalytic system is obtained when 10 mol% BiOCl is supported on MgO with 10 mol% Li 2 CO 3 , which leads to a methane conversion of 18%, C 2 selectivity of 83%, and an ethylene-to-ethane molar ratio of 2.9 for at least 12 h under the aforementioned conditions and atmospheric pressure. The unsupported or supported samarium chloride free of Li 2 ,CO 3 was less effective under similar conditions. Only when the samarium chloride and lithium carbonate contents on the support were sufficiently increased (28 and 40 mol%, respectively) the system became effective towards high C 2 selectivity and stability. In contrast, none of the manganese-chloride-based systems exhibited good C 2 selectivity and stability except initially, but they mainly promoted the reaction of methane to carbon oxides. The presence of chlorine, the nature of the cation associated with it and lithium are found to be key factors in determining the performance of the catalysts. The introduction of Li 2 CO 3 is found to retard the loss of surface chlorine and prevent the decrease of surface bismuth and samarium, resulting thereby in more stabilized systems. In addition, the bulk and surface modifications, which are more prominent in the presence of Li 2 CO 3 , caused by calcination and reaction conditions are believed to influence the formation of the catalytically active or inactive sites. The performance of the catalysts is related to its surface composition, bulk modification, decomposition, and reducibility of the metal chlorides or oxychloride on the basis of XPS, XRD, SEM, and thermal analysis (TPD and TPR) investigations.

reported by 2 patients (22%), but were not considered drug-related. No DLT has been observed to date. Of 8 patients evaluable for efficacy, the best responses were: complete response (n = 1), partial response (n = 1), minimal response (n = 2), stable disease (n = 2), and progressive disease (n = 2). Conclusion: These preliminary data suggest that vorinostat plus lenalidomide and dexamethasone represents a novel oral combination therapy that is active and relatively well tolerated in the treatment of relapsed or refractory multiple myeloma. Enrollment is ongoing and study updates will be presented.

The catalytic behaviour of iron-based mono-and bimetallic systems on different supports was studied in the Kolbel—Engelhardt (KE) synthesis at 498–598 K and atmospheric pressure with a fixed bed flow reactor (CO/H 2 O=3). In the case of monometallic catalysts the activity was found to be dependent on the nature of the support, the pretreatment condition, the contact time and the reaction temperature. The most active catalyst were those supported on low surface area supports (e.g. SiO 2 , TiO 2 , ZrO 2 ). Such catalysts were easily reducible and showed good crystalline structure, unlike those supported on high surface area samples (SiO 2 40A, γ-Al 2 O 3 , MgO). Alloying iron with cobalt noticeably enhanced activity, selectivity and stability of all catalysts independent of the supports. The product distribution was shifted to higher hydrocarbons and selectivity to olefin formation increased. It is proposed that the major portion of hydrocarbons produced in the KE reaction was via a sequential reaction pathway involving the water-gas shift reaction followed by the Fischer-Tropsch reaction.

A new method of preparation of heterogeneous catalysts, derived from the intermetallic hydrides of ZrNiHx, ZrCoHx, HfNiHx, HfCoHx, ZrFeHx, ZrNiCuHx, ZrCoCuHx, TiCuHx and TiMoHx (0.5 ⩽ x ⩽ 3), has been recently developed. The phenomenon of surface segregation of metals due to oxidation serves as the basis of the method. It was established that the effect of the surface segregation due to the oxidation is enhanced by the influence of hydrogen, evolved from the bulk of the hydrides. The catalysts derived from the intermetallic hydrides are shown to be quite active in the reactions of hydro-dehydrogenation, hydrogenolysis, dehydrocyclization and hydrodealkylation of hydrocarbons. These catalysts are more active than those of the individual as well as supported metallic catalysts in comparable conditions. Moreover, these systems exhibit higher stability in all the investigated reactions. A mechanism has been proposed for the formation of the catalytically active surface on the intermetallic hydrides.

Plasma immunoreactive insulin levels were measured before and for 6 hr following a 100 g oral glucose load in ten normal volunteers and 17 grossly obese subjects. Eleven of the obese had an abnormal glucose tolerance, five of whom were overt diabetics. Twelve of the obese were restudied after significant weight reduction (thinned obese). Eight thinned obese subjects were also restudied 6–12 mo after completion of the weight reduction protocol. Body composition was measured in each subject prior to testing. Obesity was associated with hyperinsulinemia in the fasting state and in response to oral glucose. The obese diabetics demonstrated a delay and an impairment of insulin secretion in response to glucose. After weight reduction, elevated fasting plasma insulin levels fell in all. Insulin response to oral glucose was not different in the thinned obese with normal glucose tolerance from that observed in the normal volunteers. There was significant correlation between both fasting plasma insulin and total measurable insulin following the glucose load, and total body fat in the obese and thinned obese nondiabetics, but not in the obese overt diabetics. There was, however, significant correlation between fasting plasma insulin levels and total body fat in the diabetics who had a normal fasting blood sugar. These data indicate that the hyperinsulinemia of obesity is clearly related to the increase in total body fat. Carbohydrate intolerance occurs in those obese individuals with a limited pancreatic insulin secretory reserve, which fails to compensate for the increase in total body fat.