Následující kazuistické sdělení popisuje případ 66leté ženy došetřované pro bolesti břicha a dilataci kalichopánvičkového systému. Vzhledem k nálezu prostřednictvím zobrazovacích metod bylo vysloveno podezření na primární nádorové onemocnění vývodného močového systému. Bioptické vyšetření překvapivě odhalilo extramedulární postižení mnohočetným myelomem. Během dalšího došetřování byla pomocí cytogenomických metod nalezena raritní chromozomální aberace t (6; 22).
The following case report describes a 66-year-old woman who presented with abdominal pain and renal pelvis dilatation. Based on imaging methods, a primary urinary system tumor was suspected. However, targeted biopsy surprisingly revealed the presence of extramedullary multiple myeloma. The patient was then found to harbor a rare chromosomal aberration t (6; 22).
- Klíčová slova
- extramedulární postižení, cytogenomika, FISH,
- MeSH
- diagnostické zobrazování metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * diagnóza patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Although novel therapies improved prognosis of multiple myeloma (MM) patients, clinical outcomes in the multi-refractory population are still poor. PATIENTS AND METHODS: We reviewed data from the Czech Registry of Monoclonal Gammopathies, identified and characterized triple-class exposed (3CE) relapsed/refractory MM patients, treatment patterns after 3CE, assessed overall survival (OS), progression-free survival (PFS), time to next treatment (TTNT), explored cohorts with and without triple- and penta-refractoriness. RESULTS: In 83 3CE patients who started subsequent therapies, the median OS was 14.2 months (95% CI, 8.5-19.9), PFS 6.2 months (95% CI, 3.9-8.5), and TTNT 7.2 months (95% CI, 4.6-9.8). Triple- and penta-class refractory patients had a significantly worse prognosis in all outcomes. Their life expectancy was shorter, the disease progression started earlier, and the TTNT was shorter, which increased likelihood of becoming refractory to more therapies. Time-to-event results from the first index date and all index dates analyses were very similar. CONCLUSION: Similar to previous studies from the US and Europe, our results show a high disease burden. Introduction of novel therapies, such as CAR-T cells, new bispecific and trispecific monoclonal antibodies, and other drugs, is expected to bring significant benefits to these patients.
- MeSH
- doba přežití bez progrese choroby MeSH
- lidé MeSH
- mnohočetný myelom * farmakoterapie MeSH
- registrace MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- dexamethason terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- mnohočetný myelom * farmakoterapie MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- MeSH
- antitumorózní látky klasifikace terapeutické užití MeSH
- biologická terapie * klasifikace MeSH
- humanizované monoklonální protilátky klasifikace terapeutické užití MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé MeSH
- primární amyloidóza * farmakoterapie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
We performed real world evidence (RWE) analysis of daratumumab, lenalidomide and dexamethasone (Dara-Rd) versus lenalidomide and dexamethasone (Rd) treatment in relapsed/refractory multiple myeloma patients (RRMM). In total, 240 RRMM patients were treated with Dara-Rd from 2016 to 2022 outside of clinical trials in all major Czech hematology centers. As a reference, 531 RRMM patients treated with Rd were evaluated. Patients' data were recorded in the Czech Registry of Monoclonal Gammopathies (RMG). Partial response (PR) or better response (ORR) was achieved in significantly more patients in Dara-Rd than in Rd group (91.2% vs. 69.9%; p < 0.001). The median progression free survival (PFS) was 26.9 months in the Dara-Rd and 12.8 months in the Rd group (p < 0.001). Median overall survival (OS) was not reached in the Dara-Rd compared to 27.2 months in the Rd group (p = 0.023). In patients with 1-3 previous treatment lines, there was significant PFS benefit of Dara-Rd compared to Rd (median PFS not reached vs. 13.2 months; p < 0.001). In patients with > 3 previous treatment lines, there was no significant PFS benefit of Dara-Rd treatment (7.8 months vs. 9.9 months; p = 0.874), similarly in patients refractory to PI + IMIDs (11.5 months vs. 9.2 months; p = 0.376). In RWE conditions, the median PFS in RRMM patients treated with Dara-Rd is shorter when compared to clinical trials. In heavily pretreated RRMM patients, efficacy of Dara-Rd treatment is limited; best possible outcomes of Dara-Rd are achieved in minimally pretreated patients.
- MeSH
- farmakoterapie metody MeSH
- imunoglobuliny analýza MeSH
- lidé MeSH
- primární amyloidóza * diagnóza terapie MeSH
- Check Tag
- lidé MeSH
AL amyloidóza (light chain) je systémové nebo orgánově limitované onemocnění patřící do skupiny mono-klonálních gamapatií, resp. plazmocelulárních dyskrazií. Onemocnění je charakterizované depozicí fibril tvořených fragmenty nebo kompletními molekulami monoklonálních lehkých řetězců imunoglobulinu produkovaných klonální plazmocelulární populací. Inhibice tkání amyloidem má za následek progredující postižení orgánů nejčastěji ledvin, srdce, jater a periferního nervového systému. Diagnostika AL amyloidózy zahrnuje komplexní vyšetření zahrnující průkaz monoklonálního imunoglobulinu v séru a/nebo v moči či strukturálních podjednotek volných lehkých řetězců imunoglobulinu, průkaz produkujícího B buněčného klonu a orgánový screening. Nezbytností je bioptický odběr tkáně s histologickým průkazem a typizací amyloidových mas. Léčba AL amyloidózy je přísně individuální s volbou terapie s ohledem na věk, komorbidity a pokročilost orgánového postižení. Eliminace B lymfocytárního klonu a redukce nálože amyloidogenních lehkých řetězců (tedy dosažení hematologické remise) je podmínkou k dosažení orgánové léčebné odpovědi a tím i delšího přežití nemocných. Doposud nejúčinnější léčebnou modalitu pro nemocné s AL amyloidózou představuje terapie vysokodávkovaným melphalanem s podporou auto logního štěpu. Tato léčebná modalita je spojena s vysokým procentem dosažených remisí, nicméně tuto terapii lze poskytnout pouze asi 20 % pacientům. Pro indukční terapii před autologní transplantací stejně jako pro konvenční terapii u netransplantabilních nemocných se v současnosti používá režim kombinující monoklonální protilátku daratumumab s bortezomibem, cyclophosphamidem a dexamethasonem. Léčba je u většiny pacientů spojena s vysokým procentem hematologických, ale i orgánových odpovědí při velmi dobré toleranci. Pro léčbu relabujících či refrakterních nemocných je užíváno režimů s alkylačními cytostatiky, imunomodulačními léky či venetoclaxem. V současnosti probíhají klinické studie testující terapeutické použití protilátek vůči amyloidovým depozitům v tkáních. Nedílnou součástí léčby je podpůrná terapie cílená na zlepšení či náhradu funkce postižených orgánů, nezbytná je mezioborová spolupráce.
AL amyloidosis (light chain) is a systemic or organ-limited disease belonging to the group of monoclonal gammopathy, or plasma cell dyscrasias. The disease is characterized by the deposition of fibrils formed by fragments or complete molecules of monoclonal immunoglobulin light chains produced by a clonal plasma cell population. Inhibition of tissues by amyloid results in progressive involvement of organs most often the kidneys, heart, liver, and peripheral nervous system. The diagnosis of AL amyloidosis includes a comprehensive examination including the detection of monoclonal immunoglobulin in serum and/or urine or structural subunits free light chains of immunoglobulin, the detection of a producing B cell clone and organ screening. A tissue biopsy with histological proof and typing of amyloid masses is a must. The treatment of AL amyloidosis is strictly individual with the choice of therapy considering age, comorbidities and advanced organ involvement. The elimination of the B lymphocyte clone and the reduction of the load of amyloidogenic light chains (i.e., the achievement of hematological remission) is a condition for achieving an organ treatment response and thus longer patient survival. To date, the most effective treatment modality for patients with AL amyloidosis is high dose melphalan therapy with autologous graft support. This treatment modality is associated with a high percentage of remissions achieved; however, this therapy can only be given to about 20% of patients. For induction therapy before autologous transplantation, as well as for conventional therapy in non-transplantable patients, a regimen combining the monoclonal antibody daratumumab with bortezomib, cyclophosphamide and dexamethasone is currently used. In most patients, the treatment is associated with a high percentage of hematological and organ responses with very good tolerance. For the treatment of relapsing or refractory patients, regimens with alkylating cytostatics, immunomodulating drugs or venetoclax are used. Clinical trials are currently underway testing the therapeutic use of antibodies against amyloid deposits in tissues. An integral part of the treatment is supportive therapy aimed at improving or replacing the function of the affected organs, interdisciplinary cooperation is essential.
- Klíčová slova
- daratumumab, venetoclax,
- MeSH
- imunoglobuliny analýza MeSH
- imunomodulační látky terapeutické užití MeSH
- inhibitory proteasomu terapeutické užití MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- primární amyloidóza * diagnóza terapie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients. METHODS: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients. RESULTS: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching ≥VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1-3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months (p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p ˂ 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months (p = 0.001), and median OS was 13.2 vs. 51.7 months (p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab-16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up. CONCLUSIONS: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies.
- Publikační typ
- časopisecké články MeSH
CONTEXT: Achieving minimal residual disease negativity (MRD-) in MM is associated with improved survival. Isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) is approved for relapsed MM patients after ≥1 prior therapy, based on IKEMA interim analysis (NCT03275285). OBJECTIVE: Report updated, longer-term depth of response (DoR) results from IKEMA, including MRD-status. DESIGN AND PATIENTS: IKEMA, a randomized, open-label, multicenter Phase 3 study, investigates Isa-Kd (n=179) versus Kd (n=123) in relapsed MM patients with 1-3 prior lines of therapy. INTERVENTIONS: IV Isa 10 mg/kg was given QW for 4 weeks, followed by Q2W. Both arms received an approved schedule of K (IV) and d (oral/IV). MAIN OUTCOME MEASURES: This prespecified analysis evaluated PFS (primary endpoint) at 159 events; secondary endpoints were ≥CR (+stringent CR), MRD-, and ≥CR+MRD-rates, as determined by IRC based on central laboratory data and review of local radiology. MRD status was assessed by NGS (sensitivity threshold ≥10-5) in bone marrow aspirates from patients achieving ≥VGPR. HYDRASHIFT Isa immunofixation (IFE) test, removing Isa interference in IFE, was used to update ≥CR rate. Secondary endpoints were compared between treatment arms using Cochran-Mantel-Haenszel test. One-sided descriptive P-values were provided. All randomized patients not reaching MRD- or without MRD assessment were considered MRD+. RESULTS: At cutoff (14-Jan-2022), with a median follow-up of 44 months, deeper responses were observed in Isa-Kd versus Kd, ≥CR rates 44.1% versus 28.5% (OR: 2.09; 95%CI=1.26-3.48; descriptive P=0.0021). For Isa-Kd versus Kd patients, MRD- (10-5) occurred in 33.5% versus 15.4% (OR: 2.78; 95%CI=1.55-4.99; descriptive P=0.0002), with 26.3% versus 12.2% reaching ≥CR+MRD- (10-5; OR: 2.57; 95%CI=1.35-4.88; P=0.0015); MRD- at 10-6 sensitivity occurred in 10.6% versus 3.3%. MRD- versus MRD+ patients (10-5) had longer mPFS (months); Isa-Kd: not calculable ([NC]; 95%CI=NC-NC) versus 21.7 (95%CI=16.4-27.1); Kd: NC (95%CI=29.2-NC) versus 16.2 (95%CI=13.4-19.5). CONCLUSIONS: These results demonstrate clinically meaningful improvement in DoR with Isa-Kd versus Kd. Impressive ≥CR and ≥CR+MRD- (10-5) rates in Isa-Kd versus Kd are the highest reported for proteasome inhibitor-based regimens in relapsed MM. Achieving MRD- led to better outcomes in both arms; Isa-Kd patients had >2-fold higher likelihood of achieving MRD-. Additionally, Isa improved outcomes of MRD+ patients.
- MeSH
- dexamethason škodlivé účinky MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory proteasomu terapeutické užití MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- mnohočetný myelom * MeSH
- oligopeptidy MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
