Research Spotlight

Auner, H.W., Gavriatopoulou, M., Delimpasi, S., Simonova, M., Spicka, I., Pour, L., Dimopoulos, M.A., Kriachok, I., Pylypenko, H., Leleu, X., Doronin, V., Usenko, G., Hajek, R., Benjamin, R., Dolai, T.K., Sinha, D.K., Venner, C.P., Garg, M., Stevens, D.A., Quach, H., Jagannath, S., Moreau, P., Levy, M., Badros, A., Anderson, L.D., Jr., Bahlis, N.J., Facon, T., Mateos, M.V., Cavo, M., Chai, Y., Arazy, M., Shah, J., Shacham, S., Kauffman, M.G., Richardson, P.G. and Grosicki, S. (2021). “Effect of age and frailty on the efficacy and tolerability of once-weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma.” Am J Hematol 96(6): 708-718.

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Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p = .024), ≥VGPR (OR, 1.68, p = .027), PFS (HR 0.55, p = .002), and improved OS (HR 0.63, p = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p = .08) and OS (HR 0.62, p = .062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p = .0060) and frail patients (15% vs. 44%; p = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM.

Nizamuddin, I., Kourkoumpetis, T., Wood, C.G. and Levitsky, J. (2021). “An Unusual Cause of Acute Pancreatitis in a Liver Transplant Recipient.” Transplant Direct 7(5): e694.

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Posttransplant lymphoproliferative disorder (PTLD) in liver transplant recipients is relatively uncommon, with an estimated incidence of 1%-3%. Retrospective reviews of liver transplant recipients have mainly reported posttransplant lymphoproliferative disorder affecting the liver, gastrointestinal tract, or lymph nodes. In this case report, we describe a 45-y-old female with a history of deceased donor liver transplantation for autoimmune hepatitis who had recurrent hospital admissions for acute pancreatitis. Ultimately, imaging revealed numerous complex pancreatic and peripancreatic masses, appearing to originate from pancreatic lymphoid tissue. Tissue biopsy later confirmed monomorphic Epstein-Barr virus-negative large B-cell lymphoma. Overall, PTLD involving the pancreas after liver transplantation is incredibly rare. The patient’s cumulative immunosuppression drug dose and time posttransplant were suspected to be her main risk factors, given that she had been exposed to several years of treatment with tacrolimus, azathioprine, mycophenolate mofetil, and prednisone. She was treated with rituximab monotherapy and later escalated to chemoimmunotherapy due to lack of response. PTLD involving the pancreas is an unusual cause of pancreatitis and should be considered in cases of recurrent pancreatitis in transplant recipients.

Hobson, D.T.G., Kinman, C.L., Gaskins, J.T., Francis, S.L., McKenzie, C.M., Stewart, J.R., Gupta, A.S. and Meriwether, K.V. (2021). “Comparative analyses of attitude, knowledge, and recollection of preoperative counseling regarding pelvic mesh among women with or without a mesh-related complication.” Arch Gynecol Obstet 303(5): 1263-1270.

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PURPOSE: Our objective was to compare the recollection of preoperative counseling regarding mesh for pelvic organ prolapse (POP) and/or stress urinary incontinence (SUI) among women with or without a mesh-related complication (MRC). We hypothesized that the patients who had MRC would better recollect counseling regarding complications associated with mesh. METHODS: We conducted a retrospective cohort study among women who had prior implantation of synthetic, non-absorbable mesh for POP and/or SUI at least 3 months prior who presented with or without a MRC. The primary outcome was the proportion of women who recalled being counseled preoperatively about the risk of mesh exposure. RESULTS: Ninety-six women were included in the final analysis (50 MRC; 46 no MRC). MRC women presented further in time from the index surgery [median 69 months [IQR 26-115] vs 12 months (IQR 6-64), p < 0.01]. After adjustment for time since surgery and age, MRC women were significantly less likely to recall being counseled about the possibility of any MRC [19/50 (38%) vs 32/44 (73%), aOR 0.29, 95% CI 0.11-0.79, p = 0.01]. They were also less likely to report they would undergo the same surgery again 5-point Likert scale [median 3 (IQR 1-4) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01], less satisfied with their mesh surgery [median 1 (IQR 1-3) vs 5 (IQR 3-5), 5-point Likert scale, p < 0.01] and recommended improved preoperative counseling [27/50 (54%) vs 6/46 (13%), p < 0.01]. CONCLUSION: Women who experienced MRC were less likely to recall being counseled about the possibility of MRC and report more unmet needs regarding perioperative counseling than women without MRC.

York, J.R., Testa, G., Gunby, R.T., Putman, J.M., McKenna, G.J., Koon, E.C., Bayer, J., Zhang, L., Gregg, A.R. and Johannesson, L. (2021). “Neonatal Outcomes after Uterus Transplantation: Dallas Uterus Transplant Study.” Am J Perinatol.

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OBJECTIVE:  Limited data are available on the outcome of infants born after uterus transplantation. Our aim was to describe the hospital course and laboratory findings in the first 2 months of life of the 12 infants born in the Dallas UtErus Transplant Study (DUETS). STUDY DESIGN:  Based on the trial protocol, information about infants was collected in a prospective fashion, including infant demographics, hospital course, and laboratory values. RESULTS:  Twelve infants were delivered, all by cesarean section, from 11 mothers who had undergone uterus transplantation (one mother had two pregnancies and delivered two babies). All pregnancies were singleton. The mothers received immunosuppressive therapy, and one had a rejection episode that was detected during pregnancy. The rejection episode resolved after steroid treatment. The infants had a median gestational age of 36(6/7) weeks (range: 30(6/7)-38(0/7) weeks) and median birth weight of 2,920 g (range: 1,770-3,470 g). The lowest Apgar’s score at 5 minutes was 8. All infants were appropriate size for gestational age. Two infants presented with bandemia but negative blood cultures. At 2 months of age, all infants achieved the developmental and behavioral milestones outlined by the American Academy of Pediatrics. CONCLUSION:  The 12 infants born from mothers with uterus transplants had a neonatal course that reflected the gestational age at delivery. No baby was born with an identified malformation or organ dysfunction. Longer follow-up and a larger number of infants are needed to confirm these observations. KEY POINTS: · Normal fetal development after uterus transplantation.. · No baby was born with malformations or showed any organ dysfunction.. · At 2 months, all infants achieved appropriate developmental and behavioral milestones..

Izekor, B.E., Kulkarni, P., Powell, P.R., Hall, J. and Garland, R.C. (2021). “Relapsing Multiple Myeloma Presenting as Cardiac Tamponade and Obstructive Uropathy.” Cureus 13(4): e14503.

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Cardiac tamponade is a rare manifestation of relapsing extramedullary multiple myeloma and portends poor prognosis. No cases of cardiac tamponade with co-occurring renal obstruction from plasmacytoma have been reported in the literature, making this case a unique presentation of relapsing multiple myeloma. The presence of known malignancy should not limit our differential diagnosis when evaluating patients with signs of cardiac tamponade.