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АнтиCD38 моноколональные антитела в множестве миеломы и за ее пределами: иммунотерапевтические механизмы, зрелость улик и клиническое позиционирование.

АнтиCD38 моноколональные антитела стали центральной иммунотерапевтической платформой во множестве миэломы, где они изменили курс лечения от рецидива или рефракторного заболевания, передней терапии, интенсификации технического обслуживания и минимального управления, ориентированного на остаточные заболевания. Их успех в многочисленных миеломах также стимулировал более широкое развитие в области иммуноглобулинового светового амилоида, отдельных гематологовых магнелез и юморальных иммунных расстройств. CD38 функционирует как как поверхностная мишень, так и как эктоэнзим, связанный с метаболизмом

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… Future challenges include sequencing after frontline CD38 exposure, retreatment, de-escalation, and integration with emerging immune-based approaches. … Clinical evidence for anti-CD38 retreatment remains limited. In a retrospective study of 43 patients with daratumumab-refractory multiple myeloma, daratumumab-based retreatment in combination with other anti-myeloma agents produced a response rate of 49% and a median PFS of 7.97 months ( 124 ). …

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms.

Opinion statementNeuroendocrine neoplasms (NEN) are a heterogeneous group of tumours derived from cells of neuroendocrine origin and can potentially arise everywhere in the human body. The diagnostic assessment of NEN can be performed using a variety of PET radiopharmaceuticals. Well-differentiated NEN (NET) present a high expression of SSTR (somatostatin receptors) and can therefore be studied with 68Ga-DOTA-peptides ([68Ga]Ga-DOTANOC, [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTATATE). Current guidelines recommend the use of SSTR imaging to assess disease extension at staging/restaging, follow-up, assessm

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… The decision to retreat patients with a 2nd or even a 3rd course was mainly based on combination of the duration of response, toxicity and degree of uptake on SSTR-PET/CT. Patients who developed progression within 12 months were excluded from retreatment [ 19 ••]. … In a recent meta-analysis, 13 studies described that PRRT retreatment was associated with an acceptable safety profile and promising efficacy: in patients with progressive GEP-NET who received retreatment with [177Lu]Lu-DOTATATE, median PFS was ≥ 12 months from the time of re-treatment [ 20 ]. …

Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy.

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow

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… The ORR for the retreated patients was low at 21% (0% ≥ CR), with DOR ranging from 1.9 to 6.8 months and a median PFS of 1.0 months [ 5 ] Both patients in our study who had received ide-cel as their prior anti-BCMA CAR T attained deep responses ≥ CR when retreated with commercial ide-cel. … outcomes seen with retreatment in our real-world analysis. …

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma.

The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumab-refractory MM were subsequently enrolled in part B and treated with daratumumab (rei

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… We expected that in part B of the phase 2 study, retreatment with daratumumab alone in this daratumumab-unresponsive population would result in an ORR close to 0% (0% to 2%). We determined that for daratumumab combined with ATRA in this patient category, an ORR <15% would be unacceptable. … Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients . Br J Haematol . 2018 ; 183 ( 1 ): 60 - 67 . 30080247 10.1111/bjh.15504 PMC6220946 43. Nijhof IS , Groen RW , Noort WA , . …

Gaps and opportunities in the treatment of relapsed-refractory multiple myeloma: Consensus recommendations of the NCI Multiple Myeloma Steering Committee.

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhi

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… Few clinical trials have examined the benefit of retreating a patient with a drug to which they previously stopped responding. … Bortezomib retreatment for relapsed and refractory multiple myeloma in real-world clinical practice. Health Sci Rep. 2019;2:e104. doi: 10.1002/hsr2.104. 15. Terpos E, Gobbi M, Potamianou A, Lahaye M, Couturier C, Cavo M. …

European experience of cladribine tablets in elderly patients with multiple sclerosis: Could it be the last treatment?

BACKGROUND: Recent studies support the need for early and intensive disease-modifying treatment (DMT) for patients with multiple sclerosis (PWMS). Abrupt DMT withdrawal may risk disease reactivation. Recent studies showed that MS disease activity was not rare after DMT withdrawal for PWMS aged >45/55 y. Immune reconstitution therapy (IRT) with cladribine tablets (CladT), may be an option for older PWMS who wish to stop DMT. OBJECTIVE: We retrospectively analysed PWMS aged >45 y who initiated CladT in 6 MS centers in Europe. RESULTS: One hundred and twenty nine PWMS (95 women/34 men, mean age

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… Patients’ clinical parameters analyzed were: age, sex, disease duration, last treatment used before CladT (if any), time duration between stopping the last treatment and CladT, retreatment with CladT, or switch to another treatment during the follow-up period. … A longer follow-up will determine whether these patients will need to be retreated in subsequent years. …

Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study.

BACKGROUND: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible. METHODS: All participants received previous curative intent treatment with radioth

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… Efforts to reduce the acute and long-term tissue injury profile by radiation with highly conformal techniques, including proton therapy, are important in the retreatment setting. … We hypothesize that CLR 131 will reduce the overall dose of EBRT required for retreatment and thereby reduce the acute and long-term toxicities that are commonly associated with standard re-irradiation treatment. …

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations.

We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.0

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… Retreatment with bortezomib-containing regimens were administered as rescue therapy in 25 (17.3%) patients, eleven (16.4%) in the VMP group and 14 (18%) in the VTP groups. … Although a substantial number of different regimens and schedules were used for the treatment of first relapse, lenalidomide-based were the most commonly used combinations for treatment at relapse (53.8% of patients) and 17.3% were retreated with bortezomib at time of relapse. …

Outcome after Surgery for Metastases to the Pelvic Bone: A Single Institutional Experience.

BackgroundThe pelvic bone is the most common site of bone metastases following the axial skeleton. Surgery on the pelvic bone is a demanding procedure. Few studies have been published on the surgical outcomes of metastasis to the pelvic bone with only small numbers of patients involved. This study sought to analyze the complications, local progression and survival after surgery for metastasis to the pelvic bone on a larger cohort of patients.MethodsWe analyzed 83 patients who underwent surgery for metastases to the pelvic bone between the years 2000 and 2015. There were 41 men and 42 women wit

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… Retreatment rates were significantly higher in patients with single bone metastasis ( p = 0.013) and in patients with initial tumor size ≤ 6.8 cm ( p = 0.021). … The mean survival time from local progression was longer in patients who received retreatment than those who did not receive retreatment (17 months vs. 5 months). Survival At the time of analysis, 55 patients (66%) had died of disease and 28 were alive. …

Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. … ople, number of eyes not specified) compared botulinum toxin with surgery in children that required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that children who received botulinum toxin may have a similar or slightly reduced chance of achieving ocular alignment (pooled risk ratio (RR) 0.91, 95% confidenc …

The Cost of Biological Terrorism.

Most Americans are or will be facing a threat more real than crimes or terrorism-it is the threat of cancer. Indeed, one-fourth of all Americans alive today will ultimately die from cancer. Yet the level of funding for cancer research in 1998 and beyond remains in doubt. The Senate Appropriations Committee has proposed a higher funding figure than the House and the difference will be resolved in negotiations this September. President Clinton has recommended a meager 2.5% increase in spending on cancer. This sum is simply not enough. Although Americans may fool themselves into thinking the gove

Current multiple myeloma treatment strategies with novel agents: a European perspective.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are be

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… Retreatment with bortezomib was examined in the prospective phase II Retreatment after Initial Response to Velcade® (RETRIEVE) study, in which patients whose disease had responded to previous bortezomib treatment and relapsed after ≥6 months could be retreated with bortezomib (with or without dexamethasone … Alternatively, retreatment with bortezomib may be considered if a good response to the initial bortezomib therapy was obtained and if the treatment-free interval was long. …

Genomic profiling enables personalized strategies to overcome drug resistance in multiple myeloma.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. It is a complex and heterogeneous disease that primarily affects older adults and is associated with significant morbidity and mortality. Despite advances in treatment, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, MM remains largely incurable, with most patients experiencing relapse and disease progression. The disease’s biological complexity is driven by a multitude of genetic and molecular alterations, which contr

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… To be distinct from prior reviews that catalog mechanisms, we synthesize genomic examples into a practical, clinician-oriented framework that shows exactly how a genomic finding changes management (e.g., PSMB5 mutations → PI selection; CRBN truncation → avoid IMiD retreatment). … Retreating with agents from a different drug class or combination, or using newer drugs, is standard [ 56 ]. Figure 1 provides a schematic overview of the major drug classes used in MM treatment. …

Analysis of the Factors Influencing Enterprise and Government Participation in the Medicines Patent Pool Based on System Dynamics Model.

BackgroundThe participation of enterprises and governments in the Medicines Patent Pool (MPP) improves the disease management levels by enhancing the accessibility of medical resources. Non-participation of the stakeholders restricts the development of the MPP. Hence, systematic analysis of the key factors influencing MPP participation is necessary.MethodsA system dynamics model of the market before and after enterprises and governments join the MPP was constructed by considering the economic benefits of both stakeholders. The effects of generic drug prices, royalty rates, pooling subsidies, a

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… The probability of new patients accepting the patent drugs of enterprises in the MPP, the probability of patients undergoing other treatments to change their treatment plan, and the probability of retreatment of rejected patients could be determined by the attraction of the patent drug in the MPP. … Here, up(t) is the sum of the potential sales volumes of drugs in unit time and number of retreatment patients. …

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women of reproductive age, causing them physical problems, … wound). The initial cost of endometrial destruction is lower than that of hysterectomy but, because retreatment is often necessary, the cost difference narrows over time.

[Exogenous re-infection in tuberculosis].

Patients infected by tuberculosis (TB) had been thought to never experience exogenous re-infection. However, exogenous re-infection in HIV-positive patients is well known. Thanks to the introduction of histopathological examination, analysis of similarities in drug-resistance patterns and epidemiological surveys of genetic phage typing for TB infection, we have begun to understand that even people with a normal immune system can experience re-infection. Recent advances in the techniques of restriction fragment length polymorphism (RFLP) and spoligotyping allow determination of similarities in

Краткосрочное и долгосрочное облегчение боли с помощью радиочастотной ризотомии у пациентов с множественным склерозом с тригеминальной невралгией: систематический обзор.

У пациентов с множественным склерозом (MS) тригеминальная нейронгия (TN) является изнурительным заболеванием, которое часто не дает медицинской помощи. Радиочастотная ризотомия (RFR) является широко распространенным вмешательством, однако ее результаты в этой конкретной группе населения требуют всеобъемлющего синтеза. Цель этого систематического обзора заключается в оценке краткосрочных и долгосрочных мер по облегчению боли, коэффициентов рецидива и характеристик безопасности RFR у пациентов, имеющих связанные с MS TN (MS-TN). Систематический поиск PubMed, Scopus, Web of Science и Embase был п

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… This pattern of recurrence often necessitated repeat procedures, with retreatment rates reported between 42% and 60% [ 11 , 14 - 16 ]. … This recurrence is not merely a statistical finding but has direct clinical implications, as reflected in the high retreatment rates reported, which ranged from 42% to 60% [ 11 , 14 - 16 ]. …

Spine surgery for metastatic spine cancer in the era of advanced radiation therapy.

Metastatic spine cancer (MSC), a common complication of advanced malignancies, poses significant challenges due to pain, neurological deficits, and mechanical instability. While radiation therapy is a cornerstone of treatment, the role of spine surgery is evolving, fueled by advances in surgical techniques and radiation modalities such as stereotactic body radiation therapy (SBRT). This review examines the evolving role of spine surgery in MSC management, focusing on separation surgery, surgical innovations, and future directions. The treatment paradigm for MSC shifted with the advent of SBRT,

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… Recent studies have shown that SBRT is an effective retreatment option after failed initial radiation therapy [ 17 ]. The 1-year local control rate of SBRT after EBRT failure ranges from 66% to 90% [ 33 ]. … Alghamdi et al. [ 59 ] found that surgically downgrading Bilsky grade 2 or 3 compression to grade 0 or 1 before SBRT significantly improved local control and reduced retreatment rates. …

Management of relapsed/refractory AL amyloidosis.

AbstractFrontline therapy for systemic amyloid light chain (AL) amyloidosis has evolved significantly with the approval of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone, which has significantly improved rates of both hematologic and organ responses. Despite these advances, many patients eventually relapse, and there remains no established standard salvage regimen or optimal timing. In this review, we examine optimal timing of salvage regimens and currently available therapeutic options after daratumumab failure, including next-generation proteosome inhibitors

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… Retreatment with bortezomib- or daratumumab-containing regimens may be considered in patients with prior durable response and tolerated therapy well. … Retreatment may be appropriate in patients who remain sensitive, especially those with coexisting myeloma. …

A cervical spine metastasis of a hepatocellular carcinoma: a rare presentation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with bone metastases signifying advanced disease and a poor prognosis. Although bone metastases in HCC are relatively uncommon, they present significant diagnostic and therapeutic challenges. We present a rare case of cervical spine metastasis as a presenting feature of HCC progression, highlighting the need for timely diagnosis and multidisciplinary care. CASE PRESENTATION: A 55-year-old North African female with a history of hepatitis C-related cirrhosis, successfully treated with antiviral t

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… Various RT schedules, such as 30 Gy in 10 fractions, 20 Gy in 5 fractions, and 8 Gy in a single fraction, show similar response rates and late toxicity, though single-fraction treatments often require retreatment. … Personalized RT approaches are recommended, with aggressive treatments for patients with higher survival potential and well-controlled liver disease, using a total dose of 48 Gy in 2 Gy fractions for better outcomes and fewer retreatments [ 16 ]. …