29 september 2022: Bron:  BLOOD 2022

Het toevoegen van daratumumab aan een VCd-kuur (bortezomib, cyclofosfamide en dexamethason) bij patiënten met light chain Amyloïdose verhoogt het percentage diepe hematologische responsen en meer patiënten bereiken een zeer goede partiële respons in vergelijking met patiënten die alleen een VCd-kuur krijgen. Dat blijkt uit de resultaten van de fase III ANDROMEDA  studie.

Deze ziekte is verwant aan Multiple Myeloma (ziekte van Kahler - botkanker of beenmergkanker) en ziekte van Waldenström.  Zie ook kwaadaardige plasmacelziekten


De onderzoekers hebben gerandomiseerd 388 patiënten ingedeeld in twee groepen. 1 groep kreeg alleen een VCd-kuur (bortezomib, cyclofosfamide en dexamethason). De andere groep kreeg daaraan toegevoegd daratumumab.  

  • Patiënten kregen wekelijks bortezomib (1,3 mg/m²), cyclofosfamide (300 mg/m² tot 500 mg per week) en dexamethason (20 tot 40 mg) toegediend gedurende zes cycli van 28 dagen.
  • De studiegroep kreeg ook subcutaan daratumumab (in de vorm van 1.800 mg samen met recombinant humaan hyaluronidase PH20 in 15 ml) eenmaal per week in cycli 1 en 2 en elke twee weken in cycli 3 tot en met 6.
  • Na cyclus 6 kreeg de D-VCd groep elke vier weken alleen subcutaan daratumumab, tot een totaal van 24 cycli vanaf de eerste dosis.
  • Bovendien kregen in de D-VCd-groep 149 patiënten (77,2 procent) na zes cycli alleen daratumumab; van die patiënten hadden 17 (11,4 procent) een doorlopende behandeling.

Het primaire einddoel was het totale hematologische complete responspercentage.
Secundaire einddoelen waren onder meer progressievrije respons, orgaanrespons, tijd tot hematologische respons, algehele overleving en veiligheid.
De mediane duur van de behandeling was 21,3 maanden voor D-VCd en 5,3 maanden voor VCd.

De mate van diepe hematologische responsen was beter en effectiever voor D-VCd en meer patiënten bereikten een zeer goede partiële respons ten opzichte van alleen VCd.
Specifiek, na 18 maanden, vonden de onderzoekers significant grotere percentages aan hartresponses (53 versus 24 procent) en nierresponspercentages (58 versus 26 procent) met D-VCd versus VC-d.

Het abstract van de studie werd gepubliceerd op BLOOD 2022. Voor een volledige studierapport moet betaald worden:

Abstract

In the phase 3 ANDROMEDA trial, patients treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) had significantly higher rates of organ and hematologic response compared with patients who received VCd alone. Here, we present patient-reported outcomes (PROs) from the ANDROMEDA trial. PROs were assessed through cycle 6 using three standardized questionnaires. Treatment effect through cycle 6 was measured by a repeated-measures, mixed-effects model. The magnitude of changes in PROs versus baseline was generally low, but between-group differences favored the D-VCd group. Results were generally consistent irrespective of hematologic, cardiac, or renal responses. More patients in the D-VCd group experienced meaningful improvements in PROs; median time to improvement was more rapid in the D-VCd group versus the VCd group. After cycle 6, patients in the D-VCd group received daratumumab monotherapy and their PRO assessments continued, with improvements in health-related quality of life (HRQoL) reported through cycle 19. PROs of subgroups with renal and cardiac involvement were consistent with those of the intent-to-treat population. These results demonstrate that the previously reported clinical benefits of D-VCd were achieved without decrement to patients' HRQoL and provide support of D-VCd in patients with AL amyloidosis.

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(VCd)-kuur, bortezomib, cyclofosfamide, dexamethason, multiple Myeloma, ziekte van Kahler, botkanker, ANDROMEDA fase III studie, light chain amyloidosis


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