Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. METHODS: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. RESULTS: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). CONCLUSIONS: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown. METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival. RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65). CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).

Analysis of retinal structure and function in cone dystrophy with supernormal rod response.

PURPOSE: To report the clinical and electrophysiological features of cone dystrophy with supernormal rod response (CDSRR). METHODS: Retrospective cohort study of 15 unrelated patients (nine males and six females, median age 16, range 5-47 years) diagnosed with CDSRR by clinical examination, full-field electroretinography (ERG) and genetic testing. OBSERVATIONS: History, ophthalmic examination including near vision, color vision and contrast sensitivity assessment, multimodal retinal imaging and ERG. Genetic testing was done for all patients using next-generation sequencing. RESULTS: The rate of consanguinity was 86.7%. Color vision was defective in 56.3%. Near vision was defective in all patients (mean 20/160). Contrast sensitivity was affected in all patients at low contrast of 2.5%. A parafoveal ring of increased autofluorescence imaging was seen in most patients (75%). Supernormal mixed maximal response b-wave was seen bilaterally in 63% of patients (and high normal in 37%). Rod dysfunction with prolonged rod b-wave latency was detected in all. The 30-Hz flicker response was more reduced and delayed compared to the single-flash cone response. A novel homozygous missense variant c.530G>C (p.Cys177Ser) in KCNV2 was detected in one patient, the nonsense homozygous mutation c.427G>T (p.Glu143*) was found in 13 patients, and the nonsense c.159C>G (p.Tyr53*) was found in one patient. CONCLUSION: This is the largest cohort of CDSRR from a single ethnic background. Rod dysfunction and reduced 30-Hz flicker response were demonstrated in all patients. In contrast to previous descriptions in the literature, a supernormal combined dark-adapted rod-cone ERG was present in the majority of the patients at standard stimulus intensity. Considering the consistent genotype and the demonstration of likely pathogenic genetic variants in all the patients, we argue that the combination of delayed rod b-wave and subnormal flicker response strongly suggests the diagnosis of CDSRR.

Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era.

Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.

Case report: Inferior valved for non-valved glaucoma drainage device exchange for glaucoma control and cosmesis.

Introduction: While the exchange of a superior valved glaucoma drainage device (GDD) for a non-valved GDD has been reported for achieving glaucoma control, inferior GDD exchange for improving the cosmetic appearance of the eyes due to poor appearance caused by encapsulated GDDs has not been previously documented. Here, we report on two patients with inferior valved GDDs who underwent an exchange for non-valved devices for glaucoma control and cosmetic improvement. Case description: We report on the case of a 23-year-old gentleman and that of an 8-year-old girl, both of whom had inferior valved GDDs with uncontrolled intraocular pressure and unsightly appearance due to encapsulated GDD plates within the palpebral aperture. Both patients were unhappy about the appearance of their eyes. In each case, improvements in both glaucoma control and cosmesis were achieved by exchanging the valved GDDs for non-valved ones. Conclusion: Exchanging a valved for a non-valved GDD might help improve the cosmetic appearance of the eyes, in addition to providing glaucoma control.

Lacrimal gland enlargement in inactive thyroid eye disease: a case series and literature review.

PURPOSE: This study aimed to evaluate the morphometric and volumetric dimensions of the lacrimal gland in patients with inactive thyroid eye disease and compare them with the values reported in the literature. METHODS: This case series evaluated consecutive patients with inactive thyroid eye disease treated at a tertiary eye hospital from 2015 to 2020. The patients' baseline demographics and clinical characteristics were obtained. The axial and coronal length, width, and volume of the lacrimal gland were measured on computed tomography scan images, and the results were statistically analyzed. RESULTS: A total of 21 patients (42 orbits) with inactive thyroid eye disease were evaluated. Their mean age was 49.0 ± 14.6 years, and 12 (57.1%) of them were men. The main complaint was dryness, and the majority of the patients had good vision and mild proptosis. The mean axial length and width of the lacrimal gland were 19.3 ± 3.9 mm and 7.5 ± 2.1 mm, respectively; coronal length and width, 20.4 ± 4.5 mm and 7.5 ± 2.1 mm, respectively; and lacrimal gland volume, 0.825 ± 0.326 mm3. Age, sex, or laterality were not found to be determinants of lacrimal gland enlargement. CONCLUSION: Patients with thyroid eye disease have enlarged lacrimal gland even in the nonactive phase of the disease multifactorial aspects influence the lacrimal gland in thyroid eye disease, making it difficult to establish a clear correlation with predisposing factors. Further studies are warranted to better understand the association between thyroid eye disease and the lacrimal gland.

Comparison of Patient Outcomes With Two Different Formulations of Melphalan as Conditioning Chemotherapy for Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.

BACKGROUND: High-dose melphalan (HDM) with autologous hematopoietic cell transplantation (AHCT) after induction chemotherapy is considered standard of care in transplant-eligible patients with newly-diagnosed multiple myeloma (MM). Alkeran melphalan has propylene glycol as a solvent (PG-mel) while Evomela utilizes a propylene glyclol-free formulation (PGF-mel). We evaluated the differences in efficacy and safety of the 2 formulations as there are no prospective head-to-head trials. METHODS: We retrospectively reviewed the medical records of all 259 consecutive MM patients who received PGF-mel as part of HDM-AHCT at The Ohio State University (OSU). The comparator group was the preceding 255 patients who received PG-mel. RESULTS: Baseline patient characteristics were similar between the 2 groups. Post-AHCT rates of relapse were comparable in the PG-mel and PGF-mel groups. Some adverse events were observed at a higher frequency in the PG-mel group compared to the PGF-mel group (grade ≥ 2 mucositis, febrile neutropenia, other infectious complications, and acute renal insufficiency). Time to neutrophil engraftment was slightly longer in the PG-mel group while time to platelet engraftment was longer in PGF-mel group. Red cell transfusion requirement was higher with the use of PG-mel but not platelet transfusion. Duration of hospitalization was slightly shorter with PGF-mel but readmission rates within 30 days of discharge were higher. CONCLUSION: Considering possible confounding factors could possibly account for observed differences in some adverse events, the comparable treatment responses, and difference in cost of the 2 formulation, The OSU reverted to PG-mel as the preferred formulation for HDM-AHCT in MM.

Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience.

BACKGROUND: The role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2. PATIENTS AND METHODS: We conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded. RESULTS: Fifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/m2 as conditioning regimen before infusion of a median of 3.8 × 106 CD34+ cells/kg. Fifty-eight percent patients had maintenance therapy and 81% patients attained CR/VGPR as the best response after sAHCT2. The median PFS and OS after sAHCT2 were 1.6 and 3.6 years, respectively. On multivariable analysis, high-risk cytogenetics, not having attained CR/VGPR, and having more than 2 lines of therapy post-AHCT1 were associated with inferior PFS. Melphalan 140 mg/m2 compared to melphalan 200 mg/m2 and no maintenance therapy compared to maintenance therapy were not associated with inferior PFS. There was no transplant-related mortality in this patient cohort. CONCLUSIONS: For MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.

Impact of interval progression before autologous stem cell transplant in patients with multiple myeloma.

In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.

Fitness and frailty in myeloma.

As the aging population grows, so too does the number of well-tolerated antimyeloma therapies. Physicians will see an increasing volume of patients for subsequent lines of therapy, which could now extend this relationship for over a decade. For younger patients, treatment choices are infrequently impacted by concerns of fitness, but instead about effecting the deepest, most durable response. Older adults, in contrast, are more likely to experience under- than overtreatment, and therefore more objective (and ideally straightforward) ways to evaluate their fitness and ability to tolerate therapy will increasingly assist in decision-making. Post hoc analyses categorizing the fitness of trial patients in the modern treatment era globally demonstrate that even in highly selected populations, those that are recategorized as less fit or frail are consistently at higher risk of inferior outcomes and increased toxicities. Real-world data are comparatively lacking but do demonstrate that most patients with myeloma are not representative of those enrolled on clinical trials, generally more heavily burdened by comorbidities and more likely to be categorized as "less than fit." Simultaneously, the number of therapeutic options open to patients in the relapsed setting continues to grow, now including T-cell engagers and cellular therapies, with their unique toxicity profiles. The aim of this review is to summarize the available data, highlight some of the approaches possible to easily assess fitness and how results might inform treatment selection, and illustrate ways that patients' condition can be optimized rather than lead to exclusion from the more complex therapies newly available.

Risk factors, complications, and outcomes of phacoemulsification cataract surgery complicated by retained lens fragments in Asian eyes: A 10-year retrospective study.

PURPOSE: To study the risk factors, visual outcomes, and sequelae of phacoemulsification surgery complicated by retained lens fragments (RLFs). METHODS: This single-center case-control study enrolled consecutive eyes complicated by RLF and compared them to age- and gender-matched uneventful cataract surgery cases at a tertiary care teaching hospital. Biometric, intraoperative, and postoperative data were collected. The primary outcome measures were risk factors, visual outcomes, and rate of postoperative complications. RESULTS: The study and control groups included 282 and 289 eyes, respectively. The estimated incidence of RLF was 1.47% during the study. We found a statistically higher risk of RLF among diabetics (P < 0.001), those with a history of intravitreal injections (P = 0.001), eyes with dense nuclear sclerosis, anterior capsular cataract (P < 0.001), and posterior polar cataract (P = 0.01). There was a statistically higher risk of RLF in eyes with a higher mean preoperative visual acuity (logarithm of the minimum angle of resolution) (P < 0.001) and in cases performed by trainees (P < 0.001). Most eyes in the RLF group (n = 207, 73.4%) retained their preoperative vision or experienced a one-line improvement in visual acuity and 14 eyes (5.3%) experienced more than one-line improvement in vision. CONCLUSION: Although RLFs are rare, they can affect the quality of postoperative vision and outcomes of complicated phacoemulsification surgery.

Coincident PAMM and AMN and Insights Into a Common Pathophysiology.

PURPOSE: To analyze imaging characteristics and the clinical course of patients demonstrating coincident lesions of paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) in the same eye. DESIGN: Retrospective, observational case series. METHODS: Lesions from patients presenting with coincident PAMM and AMN in the same eye were evaluated with multimodal imaging including optical coherence tomography (OCT). The association with ocular and systemic findings was also investigated. RESULTS: Fifteen subjects (17 eyes) were included in the study. The mean age was 44.4 ± 15.3 years and the follow-up period ranged from 1 to 32 weeks (mean, 11.9 ± 11.4 weeks). The mean visual acuity was 0.8 ± 0.6 logarithm of minimal angle of resolution (Snellen equivalent 20/126) at baseline and 0.3 ± 0.4 logarithm of minimal angle of resolution (Snellen equivalent 20/40) at the last follow-up. PAMM and AMN lesions occurred in the setting of Purtscher's retinopathy (4 eyes, 3 patients), retinal vein occlusion (7 eyes, 7 patients), central retinal artery occlusion (1 eye, 1 patient), and idiopathic retinal vasculitis (1 eye, 1 patient). In 4 eyes (3 patients), an association with other ocular disorders was not identified as evaluated with multimodal imaging. Of the total cohort, 11 eyes (64.7%) showed extension of the AMN hyperreflective bands in Henle's fiber layer with a Z-shaped morphology on OCT B-scan. CONCLUSIONS: The presence of coincident PAMM and AMN suggests a common pathophysiologic etiology. This may be the result of retinal vein impairment and hypoperfusion at the level of the deep retinal capillary plexus possibly leading to injury to the Müller glia or photoreceptors in Henle's fiber layer.

Manifestation of Panuveitis after Intraocular Surgery in a Child with Blau Syndrome.

Blau syndrome (BS) is a rare granulomatous disease with autosomal dominant inheritance. It is characterized by a triad of dermatitis, arthritis, and recurrent uveitis. This case presents the onset of panuveitis in BS after intraocular surgery. A 10-year-old boy presented to the outpatient clinic with retinal detachment in the left eye after 6 years following early-onset cataract surgery. Bilateral panuveitis occurred 3 weeks after surgical repair and resulted in a total visual loss in the left eye and was persistent to conventional treatment in the right eye. Genetic testing revealed a mutation in NOD2 gene. The addition of adalimumab to the treatment regimen resulted in long-term uveitis control and maintenance of 20/70 vision in the right eye. We propose that NOD2-mediated inflammatory cascade can be activated by intraocular surgery and results in the manifestation of BS.

Surgical outcomes of the Aurolab aqueous drainage implant (AADI) versus the Ahmed glaucoma valve for refractory paediatric glaucoma in Middle Eastern children.

OBJECTIVE: The Aurolab aqueous drainage implant (AADI) has the potential advantages of less encapsulation and greater cost-effectiveness than the Ahmed glaucoma valve (AGV). The aim of this study was to compare the surgical success and outcomes of the AADI compared to the AGV in Middle-Eastern children. METHODS: A comparative retrospective study of consecutive paediatric patients in a tertiary eye hospital was undertaken. Data collected included demographics, type of glaucoma, intraocular pressure (IOP), number of anti-glaucoma medications (AGMs) and any subsequent complications or further surgeries. ANALYSIS: The mean IOP, number of AGMs, surgical success and number of reoperations was compared for the two groups. Surgical success at each visit was defined as IOP of ≥6 mm Hg and ≤21 mm Hg or if the reduction of IOP was ≥20% reduced from baseline. RESULTS: A total of 126 tube surgeries (56 eyes in AADI and 70 eyes in AGV) were performed in patients aged ≤18 years from 2014 to 2019. No difference was observed in the mean IOP between the two groups except at the first month post-operative visit. After six months, the AADI group had a consistently significant lower mean number of AGMs. At last follow-up, 21 (37.5%) eyes in the AADI group were glaucoma medication-free vs 15 (21.4%) eyes in the AGV group (pp=0.047). Kaplan-Meier analysis showed equivalent cumulative probability of success at two years of 69.9% [(45.9%-84.9%)] for AADI vs 66.8% [(53.4%-77.1%])) for the AGV, respectively. Twenty-four eyes in the AGV group needed one or more subsequent surgeries, whereas 13 eyes needed one or more surgery in the AADI group. CONCLUSIONS: This study shows an acceptable safety profile for the AADI in children, with a rate of failure that is comparable to the AGV, but less need for glaucoma re-operation or glaucoma medication in the first post-postoperative year.

Real World Experience of Daratumumab: Evaluating Lymphopenia and Adverse Events in Multiple Myeloma Patients.

Multiple myeloma (MM) is an incurable disease with a limited life expectancy of five years from diagnosis. Uncontrolled disease or infections are the main causes of mortality. Daratumumab, a monoclonal antibody against CD38, is approved to treat patients with MM. Its target, CD38, is expressed not only on MM cells but also on common lymphoid precursors and subsets of normal lymphocytes. Daratumumab-induced lymphopenia is common, but its clinical significance is understudied. In this study, we report the baseline characteristics, rates of severe lymphopenia, infections, and clinical trajectory of multiple myeloma patients (n = 100) treated with daratumumab-based regimens at the Ohio State University Comprehensive Cancer Center. We discover high rates of infections, hospital utilization, and severe lymphopenia and identify risks factors for severe lymphopenia, such as low pretreatment absolute lymphocyte count (ALC) values. Severe lymphopenia persists in 23% of patients, resulting in worst survival outcomes. Our data underline the importance of monitoring ALC and consider future use of prophylactic measures or alternative regimens in subsets of MM patients.

Potential of NK cells in multiple Myeloma therapy.

Introduction: Despite rapid advances in myeloma treatment with the development of new drugs, curative therapies remain elusive. Relapsed/refractory disease related to progressive dysregulation of immune system and acquired genetic abnormalities continues to be a major obstacle in achieving cure. Immune-based therapy harnessing the host defense mechanism of natural killer (NK) cells is a promising avenue in the treatment of myeloma. Areas covered: Here, we discuss the biology and cytotoxic activity of NK cells and the potential role of these innate immune cells in defense against cancer and specifically multiple myeloma. We also discuss the role of NK cells in the anti-myeloma effects of autologous and allogeneic stem cell transplantation, various novel drugs, and treatment modalities such as chimeric antigen receptor therapy. Immune evasion, either directly or indirectly involving NK cell dysfunction, may be a key and under-recognized mechanism in myeloma progression. We reviewed extensive literature identified using the keywords immunotherapy, natural killer cells, and multiple myeloma. Expert opinion: Novel treatment approaches in myeloma utilizing the immunomodulatory and cytotoxic properties of NK cells to eradicate resistant and quiescent clones could pave the way for potentially curative interventions.

Corrigendum to "Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features".

[This corrects the article DOI: 10.1155/2018/9052314.].

The use of one muscle recession for horizontal strabismus.

PURPOSE: To evaluate the outcomes of one muscle recession for horizontal comitant strabismus at a major referral hospital in the Middle East. METHOD: Retrospective charts review of postoperative outcomes of 90 patients who had undergone one muscle recession for small to moderate angle esotropia or exotropia. Data were collected for age, vision, amblyopia, previous surgery or botulinum toxin injection, preoperative deviation, amount and type of one muscle surgery, and postoperative deviation at the initial and last (six months or more) postoperative visit. Successful alignment was defined as ±10 prism diopters (PD) of orthophoria. RESULTS: Sixty patients underwent medial rectus recession and 30 patients underwent lateral rectus recession. The average preoperative and last follow up deviation -respectively- was 24 ±â€¯6.1 PD (15-35) PD and 14.62 ±â€¯8.91 PD in the medial rectus recession group and 21.3 ±â€¯5.1 PD (12-30) and 12.60 ±â€¯8.74 in the lateral rectus recession group. The final success rates were 63.3% in both groups. CONCLUSION: Single muscle strabismus surgery to correct horizontal strabismus had a variable outcome. Larger recession may help in achieving better outcomes. Properly designed prospective studies may help in identifying the factors affecting the outcomes of single muscle strabismus surgeries.

Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features.

Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20-84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved.